Nitric oxide modulates striatal neuronal activity via soluble guanylyl cyclase: an in vivo microiontophoretic study in rats.

It is now well established that nitric oxide (NO) acts as a neuromodulator in the central nervous system. To assess the role of NO in modulating striatal activity, single-unit recording was combined with iontophoresis to study presumed spiny projection neurons in urethane-anesthetized male rats. Striatal neurons recorded were essentially quiescent and were therefore activated to fire by the iontophoretic administration of glutamate, pulsed in cycles of 30 sec on and 40 sec off. In this study, iontophoresis of 3-morpholinosydnonimine hydrochloride (SIN 1), a nitric oxide donor, produced reproducible, current-dependent inhibition of glutamate-induced excitation in 12 of 15 striatal neurons, r…

N-valproyl-L-tryptophan for CNS-targeting: synthesis, characterization and efficacy in vitro studies of a new potential antiepileptic drug.

A new aminoacidic derivative of valproic acid (VPA) has been synthesized and characterized by analytical and spectral data. The rationale for the preparation of such potential antiepileptic agent is based on the observation that chemical combination of the anticonvulsant pharmacophore, VPA with essential aminoacids could afford more effective and less toxic actives. The synthesis, characterization, physico-chemical parameters functional for crossing Blood Brain Barrier of N-valproyl-L-tryptophan (4) are reported. The Log D pH7.4 (0.3) indicates that (4) is adequate to cross biological membranes. Its chemical and enzymatic stability were assessed. The experiments indicate high stability of c…

Pregnenolone sulphate improves memory processing in early-handled female rats

Early life experiences lead to sex-specific behavioural and neurochemical changes in adulthood. Indeed, early handling enhances learning and memory in male rats (Cannizzaro et al., 2005), whereas it impairs learning performance in female adult rats, a finding that has been correlated to decreased nitric oxide (NO) production in the hippocampus (Noschang et al., 2010). Pregnenolone sulfate (PREGS) is considered as one of the most potent memory-enhancing neurosteroids, since its activity as a potent positive modulator of N-methyl-d-aspartate receptors (NMDARs) and a negative modulator of gamma-aminobutyric acid(A) receptors (GABA(A)Rs) (Vallée et al., 2001). Given these premises, this study a…

Role of nitric oxide in the controlo of maximal dentate gyrus activation by Lamotrigine in the rat

Effetti dell’influenza dell’ ossido nitrico su modelli di ipereccitabilità sperimentalmente indotta: studio elettrofisiologico comparativo in vivo e in vitro nel ratto.

Alcohol preference, behavioural reactivity and cognitive functioning in female rats exposed to a three-bottle choice paradigm.

Alcohol abuse is a substantial and growing health problem in Western societies. In the last years in vivo and in vitro studies have suggested that males and females display a different alcohol drinking behaviour, with swingeing differences not only in the propensity for alcohol use but also in the metabolic and behavioural consequences. In this study we investigated, in adult female rats, ethanol self-administration and preference pattern using a 3-bottle paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on explorative behaviour in the open field (OF), and on spatial learning and reference memory in the Morri…

Nitric oxide and brain hyperexcitability.

Nitric oxide (NO) is a gaseous messenger involved in atypical forms of intercellular communications, able to exert a strong functional modulation of several neurotransmitter systems. In particular, NO heavily influences the excitatory neurotransmitter glutamate, mainly through NMDA receptors, and the inhibitory neurotransmitter GABA, mainly through GABA A receptors. Due to the involvement of glutamate and GABA in a delicate balance conditioning the functional status of the neural cells, this interaction suggests a role for NO in regulating neuronal excitability and its transition towards hyperexcitability phenomena. This article reviews the main knowledge about the relationships existing be…

Levetiracetam anticonvulsant activity is modulated by nitric oxide-active drugs in a model of partial complex epilepsy in the rat

Role of CB2 receptors and cGMP pathway on the cannabinoid-dependent antiepileptic effects in an in vivo model of partial epilepsy.

This study aimed at providing an insight on the possible role of cannabi-noid (CB) type 2 receptors (CB2R) and cGMP pathway in the antiepileptic activity ofWIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone, a non-selective CB agonist, in the maximal dentate activation (MDA) model of partial epilepsy in adult male rats. We evaluated the activity of a CB2 antagonist/inverse agonist AM630, [6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone or 6-iodopravadoline, alone or in co-administration with WIN 55,212-2. Also, in the MDA model it was investigated the co-treatment of WIN55,212…

Previous observations have suggested a role for nitric oxide in the activity of the globus pallidus, but this functional involvement has not yet been tested in vivo. The extracellular activity of single units of the globus pallidus was recorded, and neuronal nitric oxide synthase was inhibited by systemically administering 7-nitro-indazole to a group of anaesthetised rats. Forty-five per cent of cells responded with a decrease in the firing rate. In another group of rats, the microiontophoretic administration of 3-morpholino-sydnonimin-hydrocloride (a nitric oxide donor) induced an increase in neuronal firing rate (24/28 cells), whereas the administration of Nω-nitro-L-arginine methyl ester…

Effects of nitric oxide and GABA system in a rat model of temporal lobe epilepsy

Correlation of Metabolic Syndrome with Redox Homeostasis Biomarkers: Evidence from High-Fat Diet Model in Wistar Rats

Metabolic Syndrome (MetS) is an extremely complex disease. A non-balanced diet such as high-fat diet (HFD) induces metabolic dysfunction that could modify redox homeostasis. We here aimed at exploring redox homeostasis in male Wistar rats, following 8 weeks of HFD, correlating the eventual modification of selected biomarkers that could be associated with the clinical manifestations of MetS. Therefore, we selected parameters relative to both the glucose tolerance and lipid altered metabolism, but also oxidative pattern. We assessed some biomarkers of oxidative stress i.e., thiols balance, lipid peroxidation and antioxidant barriers, via the use of specific biochemical assays, individuating e…

Cannabinoid-‐mediated modulation of hippocampal hyperexcitability: focus on the interplay with nitrergic system in different rat models of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of partial complex seizure in adulthood [1]. Within the framework of hyperexcitability, growing interest has risen on the impact of cannabinoids on the control of paroxysmal phenomena [2], despite their reputation as psychotropic substances with addictive properties [3; 4]. In this regard, it was reported that the on-demand production of endocannabinoids from over-activated postsynaptic cells inhibits neurotransmitter release, hence protecting against excitotoxicity in the hippocampus [5; 6]. Nonetheless, the potential anticonvulsant action of cannabinoids has not been fully addressed. Indeed, CB-mediated effects in animal models are attr…

CNS-targeted valproic-aminoacid conjugate: preliminary studies on pharmacokinetic parameters and antiepileptic activity

Nitric oxide influence on hippocampal hyperexcitability: in vivo and in vitro comparative electrophysiological study in the rat

Being in the Past and Perform the Future in a Virtual World: VR Applications to Assess and Enhance Episodic and Prospective Memory in Normal and Pathological Aging

The process of aging commonly features a gradual deterioration in cognitive performance and, in particular, the decline of memory. Despite the increased longevity of the world's population, the prevalence of neurodegenerative conditions, such as dementia, continues to be a major burden on public health, and consequently, the latest research has been focused on memory and aging. Currently, the failure of episodic and Prospective memory (PM) is one of the main complaints in the elderly, considered among the early symptoms of dementia. It is therefore increasingly important to define more clearly the boundaries between normal and pathological aging. Recently, researchers have begun to build an…

Accumbens-caudate-septal circuit as a system for hippocampal regulation: involvement of a GABAergic neurotransmission.

Hippocampal-based epileptiform activity may reach the basal ganglia via the nucleus accumbens. Previous data suggested that caudate nucleus is able to influence hippocampal epilepsy, probably sending a projection to the septum. In order to test the hypothesis of a retrograde activation of accumbens-caudate pathway in hippocampal regulation, we electrically stimulated both caudate nucleus and nucleus accumbens and studied modifications of hippocampal EEG in the feline focal epilepsy model. We also performed bilateral electrolytic lesion of nucleus accumbens and repeated caudate stimulation. Results showed that nucleus accumbens stimulation was ineffective in modifying hippocampal epilepsy; o…

Neuronal nitric oxide synthase is involved in CB/TRPV1 signalling: Focus on control of hippocampal hyperexcitability

Cannabinoids (CB), transient receptors potential vanilloid type 1 (TRPV1) and nitric oxide (NO) were found to be interlinked in regulating some neuronal functions such as membrane excitability and synaptic transmission. TRPV1 play a fundamental role since it represents a synaptic target for CB that triggers several downstream cellular pathways. In this regard, recent evidence report that TRPV1 could influence NO production by modulating neuronal NO synthase (nNOS) activity. In the present research, we pointed to manipulate nNOS function to assess its role on TRPV1 signalling in hyperexcitability conditions elicited in the dentate gyrus of hippocampal formation. The activation of TRPV1 recep…

Modulation of in vivo GABA-evoked responses by nitric oxide-active compounds in the globus pallidus of rat.

Nitric oxide (NO) is a gaseous molecule acting as a messenger in both the peripheral and the central nervous systems. NO affects synaptic activity by modulating neurotransmitter release and/or receptor function. We previously observed that NO-active compounds modify the bioelectric activity of basal ganglia (BG) units. In this study, we applied microiontophoresis to extracellular in vivo recordings to investigate the effect of NO-active compounds on GABA-evoked responses in the globus pallidus (GP) of anesthetized rats. The changes induced by NO-active drugs on the GABA-induced inhibition were used as indicators of NO modulation. The response to GABA release was tested on recorded GP neuron…

Nitric oxide control of experimental model of partial epileptic seizures: in vivo and in vitro electrophysiological study in the rat.

Involvement of nitric oxide in maximal dentate activation, in the rat

Nitric oxide-active compounds modulate the intensity of glutamate-evoked responses in the globus pallidus of the rat

Abstract Aim The effects of local applied NO-active compounds on glutamate (GLU)-evoked responses were investigated in globus pallidus (GP) neurons. Main methods Extracellularly recorded single units from anesthetized rats were treated with GLU before and during the microiontophoretic application of S-nitrosoglutathione (SNOG), a NO donor, and Nω-nitro- l -arginine methyl ester (L-NAME), a NOS inhibitor. Key findings Most GP cells were excited by SNOG whereas administration of L-NAME induced decrease of GP neurons activity. Nearly all neurons responding to SNOG and/or L-NAME showed significant modulation of their excitatory responses to the administration of iontophoretic GLU. In these cell…

Nitric oxide-induced inhibition on striatal cells and excitation on globus pallidus neurons: a microiontophoretic study in the rat.

Single units were recorded in the striatum and in the globus pallidus (GP) of urethane-anesthetized rats under microiontophoretic administration of either Nomega-nitro-L-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), or 3-morpholino-sydnonimin-hydrocloride (SIN-1, nitric oxide, NO donor). A steady baseline firing of sporadically discharging striatal neurons (basal firing rate <0.1 spikes/s) was evoked by a pulsed microiontophoretic ejection of glutamate. On striatal neurons, microiontophoretic application of SIN-1 induced a current-dependent inhibition (11/13), whereas L-NAME administration produced a clear excitation (9/9). On GP cells, the administration of SIN-1 had …

The discharge of subthalamic neurons is modulated by nitric oxide: a microiontophoretic study in the rat

Cannabinoids, TRPV and nitric oxide: the three ring circus of neuronal excitability

Endocannabinoid system is considered a relevant player in the regulation of neuronal excitability, since it contributes to maintaining the balance of the synaptic ionic milieu. Perturbations to bioelectric conductances have been implicated in the pathophysiological processes leading to hyperexcitability and epileptic seizures. Cannabinoid influence on neurosignalling is exerted on classic receptor-mediated mechanisms or on further molecular targets. Among these, transient receptor potential vanilloid (TRPV) are ionic channels modulated by cannabinoids that are involved in the transduction of a plethora of stimuli and trigger fundamental downstream pathways in the post-synaptic site. In this…

Nitric oxide- and cGMP-active compounds affect the discharge of substantia nigra pars reticulata neurons: in vivo evidences in the rat

The nitric oxide (NO)-active drugs influence on the bioelectric activity of neurons of the pars reticulata of the substantia nigra was studied in urethane-anesthetized rats. A first group of animals was treated with 7-nitro-indazole (7-NI), a preferential inhibitor of neuronal NO synthase. In a second group of rats, electrophysiological recordings were coupled with microiontophoretic administration of Nomega-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1, a NO donor) and 8-Br-cGMP (a cell-permeable analogue of cGMP, the main second-messenger of NO neurotransmission). 7-NI and L-NAME caused a statistically significant decrease in …

Nitric oxide-active compounds modulate glutamatergic and GABAergic transmission in globus pallidus of rat

The globus pallidus (GP) of rodents, homologous to the external globus pallidus of primates, plays a critical role in the expression of basal ganglia (BG) function. Glutamatergic and GABAergic inputs have been demonstrated to greatly modulate the spontaneous GP activity. In this study the effects of local applied NO-active compounds on glutamate (GLU)- and GABA-evoked responses were investigated in rat GP neurons. Extracellularly recorded single units from anesthetized rats were treated with GLU or GABA before and during the microiontophoretic application of S-nitrosoglutathione (SNOG), a NO donor, and Nω-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Most GP cells were excited by…

3D Printing Neuron Equivalent Circuits: An Undergraduate Laboratory Exercise.

The electrical equivalent circuit for a neuron is composed of common electrical components in a configuration that replicates the passive electrical properties and behaviors of the neural membrane. It is a powerful tool used to derive such fundamental neurophysiological equations as the Hodgkin-Huxley equations, and it is also the basis for well-known exercises that help students to model the passive (Ohmic) properties of the neuronal membrane. Unfortunately, as these exercises require basic knowledge of electronics, they are generally not physically conducted in biomedical courses, but remain merely conceptual exercises in a book or simulations on a computer. In such manifestations, they l…

Antiepileptic effect of dimethyl sulfoxide in a rat model of temporal lobe epilepsy.

Dimethyl sulfoxide (DMSO) is an amphipathic molecule widely used to solubilize water-insoluble compounds. In many studies it was reported that DMSO is capable of affecting several biological processes, thus resulting in a potential cause for the misinterpretation of experimental data. Recent papers showed that DMSO modified the brain bioelectric activity in animal models of epilepsy. In an in vivo model of temporal lobe epilepsy in the rat, we examined the effects of different doses (10%, 50% and 100%) of DMSO on the maximal dentate activation (MDA). The results show that DMSO induced a dose-dependent significant reduction of the electrically induced paroxysmal activity.

Microiontophoretic Evidence that Nitric Oxide Alters Spontaneous Activity of the Substantia Nigra Pars Reticulata Neurons in the Rat

Nitric oxide-induced modulation on neuronal discharge in the basal ganglia of the rat

Dopaminergic control of feline hippocampal epilepsy: A nigrophippocampal pathway

Abstract Substantia nigra is a mesencephalic structure inserted along several circuits which appear to play a key role in epilepsy. In previous researches we postulated that substantia nigra pars compacta (SNpc) may be the site of a precise control of hippocampal epilepsy while substantia nigra pars reticulata (SNpr) may exert a modulation of both neocortical epilepsy and spreading of hyperactivity toward a motor target. In order to better understand mechanisms subserving nigral action in feline hippocampal epilepsy we electrically stimulated SNpc (dopaminergic), before and after sulpiride (dopamine receptor-antagonist) intravenous injection. Furthermore we compared hippocampal epileptiform…

Haptic Perception in Extreme Obesity: qEEG Study Focused on Predictive Coding and Body Schema

Haptic perception (HP) is a perceptual modality requiring manual exploration to elaborate the physical characteristics of external stimuli through multisensory integrative cortical pathways. Cortical areas exploit processes of predictive coding that collect sensorial inputs to build and update internal perceptual models. Modifications to the internal representation of the body have been associated with eating disorders. In the light of this, obese subjects were selected as a valid experimental model to explore predictive coding in haptic perception. To this purpose, we performed electroencephalographic (EEG) continuous recordings during a haptic task in normally weighted versus obese subjec…

TRPV1 channels in nitric oxide-mediated signalling: insight on excitatory transmission in rat CA1 pyramidal neurons

Nitric oxide (NO) is a fascinating signalling molecule implicated in a plethora of biological functions, especially at the synaptic level. Exploring neurotransmission in the hippocampus could be instrumental in the individuation of putative targets for nitric-oxide mediated neuromodulation, especially in terms of the potential repercussions on fundamental processes i.e. synaptic plasticity and excitability-related phenomena. Among these targets, endovanilloid signalling constitutes an object of study since Transient Receptors Vanilloid type 1 (TRPV1) channels possess a NO-sensitive gate modulating its activation. Also, NO has been referred to as a mediator for numerous endocannabinoid effec…

Microtubule Dynamics and Neuronal Excitability: Advances on Cytoskeletal Components Implicated in Epileptic Phenomena

AbstractExtensive researches have deepened knowledge on the role of synaptic components in epileptogenesis, but limited attention has been devoted to the potential implication of the cytoskeleton. The study of the development of epilepsy and hyperexcitability states involves molecular, synaptic, and structural alterations of neuronal bioelectric activity. In this paper we aim to explore the neurobiological targets involved in microtubule functioning and cytoskeletal transport, i.e. how dynamic scaffolding of microtubules can influence neuronal morphology and excitability, in order to suggest a potential role for microtubule dynamics in the processes turning a normal neuronal network in a hy…

Cholecystokinin-8 sulfate modulates the anticonvulsant efficacy of vigabatrin in an experimental model of partial complex epilepsy in the rat.

Summary Purpose:  We evaluated the possible additive effect induced by the administration of the anticonvulsant vigabatrin (VGB) and cholecystokinin-8 sulfate (CCK-8S) on an experimental model of partial complex seizures (maximal dentate gyrus activation, MDA). Moreover, the functional involvement of γ-aminobutyric acid (GABA) neurotransmission was tested by iontophoretically administering bicuculline (GABA receptor antagonist) in the dentate gyrus. Methods:  Urethane anesthetized rats were pretreated with VGB (50, 100 or 200 mg/kg, i.p.) or CCK-8S (8 nmol/kg, i.p.) alone or coadministered with VGB (50 mg/kg, i.p.). Dentate gyrus epileptic activity was obtained through the repetitive electr…

Lateral habenula and hippocampus: A complex interaction raphe cells-mediated

The study has shown an excitatory influence exerted by lateral habenula (LH) on hippocampal pyramidal cells. The modulatory influence is paradoxically serotonine-mediated; in fact all LH stimulation effects were abolished by intrahippocampal iontophoretic methysergide application. The data suggest the involvement of dorsal raphe nucleus. In fact, the dorsal raphe nucleus stimulation caused on hippocampus an expected inhibitory effect antagonized by intrahippocampal iontophoretic methysergide application. In the context of this neural structure we have highlighted a disinhibitory relation between two types of cells: slow serotonergic efferent neurones and fast GABAergic interneurones. The di…

Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy

The exogenous cannabinoid agonist WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), has revealed to play a role on modulating the hyperexcitability phenomena in the hippocampus. Cannabinoid-mediated mechanisms of neuroprotection have recently been found to imply the modulation of transient receptor potential vanilloid 1 (TRPV1), a cationic channel subfamily that regulate synaptic excitation. In our study, we assessed the influence of pharmacological manipulation of TRPV1 function, alone and on WIN antiepileptic activity, in the Maximal Dentate Activation (MDA) acute model of temporal lobe epilepsy. Our r…

Effects of nitric oxide-active drugs on the discharge of subthalamic neurons: microiontophoretic evidence in the rat.

The presence of nitric oxide (NO) synthase and of soluble guanylyl cyclase, the main NO-activated metabolic pathway, has been demonstrated in many cells of the subthalamic nucleus. In this study, the effects induced on the firing of 96 subthalamic neurons by microiontophoretically administering drugs modifying NO neurotransmission were explored in anaesthetized rats. Recorded neurons were classified into regularly and irregularly discharging on the basis of their firing pattern. Nω-nitro-l-arginine methyl ester (L-NAME; a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1; a NO donor), S-nitroso-glutathione (SNOG; another NO donor) and 8-Br-cGMP (a cell-permeable analogue o…

Nitric oxide influences the activity of neurones in the subthalamic nucleus of the rat.

Influence of spatial information on responses of tonically active neurons in the monkey striatum.

Influence of spatial information on responses of tonically active neurons in the monkey striatum. J Neurophysiol 95: 2975–2986, 2006. First published February 8, 2006; doi:10.1152/jn.01113.2005. Previous studies have demonstrated that tonically active neurons (TANs) in the primate striatum play an important role in the detection of rewarding events. However, the influence of the spatial features of stimuli or actions required to obtain reward remains unclear. Here, we examined the activity of TANs in the striatum of monkeys trained to make spatially directed movements elicited by visual stimuli presented ipsilaterally or contralaterally to the moving arm. Among 181 neurons responding to the…

Nitric oxide-active compounds modulate the intensity of glutamate-evoked responses in the globus pallidus

In this study, the effects of microiontophoretically applied NO-active compounds on glutamate(GLU)-evoked responses were investigated in globus pallidus (GP) neurons from anesthetized rats. Most GP cells were excited by S-nitrosoglutathione (SNOG), an NO donor, whereas administration of Nω-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, induced a decrease of GP neurons activity. Nearly all neurons responding to SNOG and/or L-NAME showed significant excitatory responses to the administration of iontophoretic GLU. In these cells, the changes induced by NO-active drugs in the magnitude of GLU-evoked responses were used as indicators of NO modulation. When an NO-active drug and GLU wer…

Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat.

The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB(1) receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB(1) antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. WIN55,212-2 (21mgkg(-1)) exerted an anticonvulsant effect, significantly reduced by the pre-treatme…

“Golden” Tomato Consumption Ameliorates Metabolic Syndrome: A Focus on the Redox Balance in the High-Fat-Diet-Fed Rat

Tomato fruits defined as &ldquo;golden&rdquo; refer to a food product harvested at an incomplete ripening stage with respect to red tomatoes at full maturation. The aim of this study is to explore the putative influence of &ldquo;golden tomato&rdquo; (GT) on Metabolic Syndrome (MetS), especially focusing on the effects on redox homeostasis. Firstly, the differential chemical properties of the GT food matrix were characterized in terms of phytonutrient composition and antioxidant capacities with respect to red tomato (RT). Later, we assessed the biochemical, nutraceutical and eventually disease-modifying potential of GT in vivo in the high-fat-diet rat model of MetS. Our data revealed that G…

Modulating Long Term Memory at Late-Encoding Phase: An rTMS Study

Despite a huge effort of the scientific community, the functioning of Long-Term Memory (LTM) processes is still debated and far from being elucidated. Functional and neurophysiological data point to an involvement of Dorsolateral Prefrontal Cortex (DLPFC) in both encoding and retrieval phases. However, the recently proposed Explicit/Implicit Memory Encoding and Retrieval (EIMER) model proposes that LTM at the encoding phase consists of anatomically and chronologically different sub-phases. On this basis, we aimed to investigate the role of right DLPFC during a late-encoding phase by means of low-frequency rTMS. Thirty right-handed healthy subjects were divided into three experimental groups…

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts

Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC) could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer's disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a pro…

Comparison of effects of Valproate and the newly synthesized Valproil-L-Tryptophan on epileptiform activity in rat brain slices

Inhibition of nitric oxide synthase influences the activity of striatal neurons in the rat

The activity of single units in the striatum of urethane-anesthetized rats was recorded before and after the systemic administration of 7-nitro-indazole (7-NI; 50 mg/kg intraperitoneally), a selective inhibitor of neuronal nitric oxide (NO) synthase. Two neuronal types were clearly distinguishable electrophysiologically, on the basis of either discharge frequency pattern or features of the individual spike waveform (spike duration, negative phase/total duration ratio, and negative phase/total amplitude ratio). Only sporadically discharging neurons (basal firing rate, <0.1 spikes/s) were influenced by 7-NI, which caused a statistically significant increase in their firing rate. In contrast, …

TRPV1 channels as putative targets in the cannabinoid-mediated synaptic activity of hippocampal neurons

Endocannabinoids (eCBs) play a critical part in pathophysiological conditions rooted on neuronal excitability such as epilepsy. eCBs seem to be involved in neuroprotection, putatively acting on the cannabinoid receptor type 1 (CB1r), but also on Transient Receptor Potential Vanilloid type 1 channels (TRPV1). Indeed, CB1r and TRPV1 are involved in the transduction of stimuli at synaptic level, though exact molecular mechanisms are far from being unveiled. Thus, we aimed to investigate the role of CB1r/TRPV1 interplay in the rat hippocampal neurotransmission by whole-cell patch clamp technique to evaluate excitatory bioelectric activity in the CA1. We pharmacologically manipulated this pathwa…

Effects of nitric oxide along basal ganglia pathways: a microiontophoretic study in the rat.

Lamotrigine and vigabatrin control of maximal dentate gyrus activation in the rat: role of nitric oxide(NO)/cGMP pathway

Nitric oxide-induced modulation of neuronal discharge in the basal ganglia of the rat

Nitric oxide modulation of direct pathway in the rat basal ganglia circuit”

The discharge of subthalamic neurons is modulated by inhibiting the nitric oxide synthase in the rat.

The effects induced on the discharge of subthalamic spontaneously active neurons by inhibiting the enzyme nitric oxide synthase was studied in two groups of urethane-anesthetized rats. In the first group of animals (n = 10), the activity of subthalamic single units was recorded before and after the systemic administration of 7-nitro-indazole (7-NI, 50 mg/kg i.p.), a selective inhibitor of neuronal nitric oxide synthase. In the second group of rats (n = 15), Nomega-nitro-L-arginine methyl ester (L-NAME), another inhibitor of nitric oxide synthase, was iontophoretically administered while performing single unit extracellular recordings. The activity of most tested spontaneously discharging ne…

Involvement of nitric oxide-soluble guanylyl cyclase pathway in the control of maximal dentate gyrus activation in the rat.

Summary Nitric oxide=soluble Guanylyl cyclase (NO=sGC) pathway on the maximal dentate gyrus activation (MDA) was studied in rats. The cerebral NO levels were modified by administrating 7-Nitroindazole (7-NI), a selective inhibitor of neuronal NOS, and L-arginine, a precursor of the synthesis of NO. 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ), a specific inhibitor of the NO-sGC pathway, was administered to study the involvement of cGMP pathway. The epileptic activity of the dentate gyrus was obtained through the repetitive stimulation of the angular bundle; MDA parameters studied were: onset time, MDA duration and post-stimulus afterdischarge (AD) duration. 7-NI caused an increase of M…

Nitric oxide affects the discharge of substantia nigra pars reticulata neurons: microiontophoretic evidences in the rat

The role of neurosteoids sulphate in a spatial and object recognition learning task

The term “neuroactive steroid” refers to steroids that have rapid modulatory effects on ligand-gated ion channels via non-genomic mechanism. Specifically, neurosteroids can alter neuronal excitability via the cell surface interacting with specific neurotransmitter receptors. The neurosteroid pregnenolone sulphate (PREGS) has been described as negative modulator of GABAA receptor and positive modulator of NMDA receptor, affecting cognition as well as emotionality. The present study was aimed to assess the effects of the acute administration of PREGS (10 mg/Kg, s. c.) on rats cognitive functions using a novel task, the Can test. This task explores, under reinforcement, the spatial/visual cues…

Polybutylene succinate artificial scaffold for peripheral nerve regeneration

Regeneration and recovery of nerve tissues are a great challenge for medicine, and positively affect the quality of life of patients. The development of tissue engineering offers a new approach to the problem with the creation of multifunctional artificial scaffolds that act on various levels in the damaged tissue, providing physical and biochemical support for the growth of nerve cells. In this study, the effects of the use of a tubular scaffold made of polybutylene succinate (PBS), surgically positioned at the level of a sciatic nerve injured in rat, between the proximal stump and the distal one, was investigated. Scaffolds characterization was carried out by scanning electron microscopy …

Evidence of a contralateral motor influence on reciprocal inhibition in man

The role of contralateral movement on both H reflex and reciprocal inhibition was studied. In normal men H reflex was induced by median nerve stimulation. Reciprocal inhibition was achieved through stimulation of the antagonist radial nerve. On this basis the effects of contralateral arm movement were analized. Furthermore the putative influence of exteroceptive origin was also verified by means of digit stimulation. Results showed that contralateral arm movement did not affect H reflex amplitude; on the contrary, it was able to enhance reciprocal inhibition induced by extensors on flexors. Study of cutaneous afferents demonstrated that contralateral digit stimulation failed to elicit modif…

Electrophysiological and Iontophoretic Aspects of the Habenular Influence on Hippocampal Neurones

In previous experimental studies, carried out on cats, we demonstrated that electrical stimulation of lateral habenula (LH) at 0.5-3.0 Hz or 5-20 Hz had a double effect (low frequency-excitation; high frequency-inhibition) on the spontaneous firing rate of single hippocampal neurones. Our results, in agreement with similar case studies, allowed us to hypothesise that in the habenular modulation of the hippocampus the raphe nucleus is probably involved. In fact, all the effects of LH stimulation were antagonised by the iontophoretic intrahippocampal application of methysergide. In the present series of experiments, performed on rats, it was possible to demonstrate that LH stimulation at 1-10…

The control of maximal dentate gyrus activation: role of nitric oxide alone and in combination with lamotrigine and vigabatrin

Reward Unpredictability inside and outside of a Task Context as a Determinant of the Responses of Tonically Active Neurons in the Monkey Striatum

Tonically active neurons (TANs) in the monkey striatum are involved in detecting motivationally relevant stimuli. We recently provided evidence that the timing of conditioned stimuli strongly influences the responsiveness of TANs, the source of which is likely to be the monkey's previous experience with particular temporal regularities in sequential task events. To extend these findings, we investigated the relationship of TAN responses to a primary liquid reward, the timing of which is more or less predictable to the monkey either outside of a task or during instrumental task performance. Reward predictability was indexed by the timing characteristics of the mouth movements. The responsive…

Ketogenic and Modified Mediterranean Diet as a Tool to Counteract Neuroinflammation in Multiple Sclerosis: Nutritional Suggestions.

Ketogenic Diet is a nutritional pattern often used as dietotherapy in inflammatory diseases, including neurological disorders. Applied on epileptic children since 1920, in recent years it has been taken into account again as a tool to both reduce inflammatory burdens and ameliorate the nutritional status of patients affected by different pathologies. Multiple sclerosis (MS) is considered an immune-mediated neuro-inflammatory disease and diet is a possible factor in its pathogenesis. The aim of this work is to investigate the main potential targets of MS-related impairments, in particular the cognitive deficits, focusing on the alteration of biomarkers such as the Brain Derived-Neurotrophic …

Intensity of GABA-evoked responses is modified by nitric oxide-active compounds in the subthalamic nucleus of the rat: a microiontophoretic study.

We have previously described modulatory effects of nitric oxide (NO)-active drugs on subthalamic nucleus (STN) neurons. In this study, the effects of microiontophoretically applied NO-active compounds on GABA-evoked responses were investigated in subthalamic neurons extracellularly recorded from anesthetized rats: 45 of 62 cells were excited by S-nitroso-glutathione (SNOG), an NO donor, whereas 28 of 43 neurons were inhibited by N-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Nearly all neurons responding to SNOG and/or L-NAME showed significant inhibitory responses to the administration of iontophoretic GABA. In these cells, the changes induced by NO-active drugs in the magnitud…

INVOLVEMENT OF NITRIC OXIDE IN MAXIMAL DENTATE GYRUS ACTIVATION IN THE RAT

Effects of nitric oxide and cGMP-active compounds on neuronal activity of substantia nigra pars reticulata: a rat in vivo study

Effects of nitric oxide influence on experimentally-induced hyperexcitability of the hippocampus: In vivo and in vitro comparative electrophysiological evaluation

NITRIC OXIDE-ACTIVE COMPOUNDS MODULATE IN VIVO GABA-EVOKED RESPONSES IN THE GLOBUS PALLIDUS OF RAT

Nitric oxide (NO) acts as a messenger in the central nervous system; it affects the synaptic activity by modulating neurotransmitter release and/or receptor function. We previously observed that NO-active compounds modify the bioelectric activity of basal ganglia (BG) units. In this study, we applied microiontophoresis to extracellular in vivo recordings to investigate the effect of NO-active compounds on GABA-evoked responses in the globus pallidus (GP) of rats. The response to GABA release was tested on recorded GP neurons before and during the administration of S-nitroso-glutathione (SNOG, NO donor) and/or Nω-nitro-L-arginine methyl ester (L-NAME), inhibitor of nitric oxide synthase (NOS…

Comparative Study of the Effects Exerted by N-Valproyl-L-Phenylalanine and N-valproyl-L-tryptophan on CA1 Hippocampal Epileptiform Activity in Rat

Background: The research on the improvement of epilepsy therapy is constantly growing. Valproyl-LPhenylalanine (VPA-Phen) and N-valproyl-L-tryptophan (VPA-Tryp) were synthesized to increase the antiepileptic efficacy of valproic acid. Methods: VPA-Phen and VPA-Tryp were comparatively tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 mM) of VPA-Phen or VPA-Tryp. Both burst duration and interburst frequency, during and after treatment, were off-line compared with baseline values. For both parameters,…

In the rat maximal dentate activation model of partial complex epilepsy, the anticonvulsant activity of levetiracetam is modulated by nitric oxide-active drugs.

The effects of nitric oxide-active drugs on the anticonvulsant action of the antiepileptic drug levetiracetam in an experimental model of partial complex seizures named maximal dentate gyrus activation were studied in rats. Levetiracetam was given alone or in combination with 7-nitroindazole, a preferential inhibitor of neuronal nitric oxide synthase, or with L: -arginine, the precursor of nitric oxide synthesis. The maximal dentate activation parameters were the time of latency and the durations of maximal dentate activation and afterdischarge responses. The administration of levetiracetam showed an anticonvulsant effect that was increased when given in combination with 7-nitroindazole. Th…

Lateral habenula and hippocampal units: electrophysiological and iontophoretic study

In previous works we studied, on cats, the effects of lateral habenula (LH) stimulation on hippocampal units. In particular, the results showed an excitation or an inhibition in relation to the stimulation frequency (0.5-3.0 Hz or 5.0-20 Hz, respectively). All the LH stimulation effects were antagonised by iontophoretic intrahippocampal application of methysergide (MS). In this series of experiments it was possible to demonstrate, on rats, that LH stimulation causes an excitatory effect in a major number of hippocampal units in relation to the frequency increase. The inhibitory effect by iontophoretic serotonine application and the reversible blockade of habenular modulation after iontophor…

Tonically Active Neurons in the Monkey Striatum are Sensitive to Sensory Events in a Manner that Reflects their Predictability in Time

It is now well established that tonically active neurons (TANs) in the monkey striatum respond to motivationally relevant sensory events, such as conditioned stimuli to which the animal had to react correctly to obtain reward. Recent findings obtained in our laboratory suggested that stimulus prediction may influence the responsiveness of the TANs. In the present study we specifically investigated the effects of temporal aspects of prediction on the responses of single TANs recorded both in the caudate nucleus and putamen of two macaque monkeys. Three different behavioral situations were employed: (1) an instrumental task, in which a visual stimulus triggering a rewarded movement was preced…

Indicaxanthin from Opuntia ficus-indica Crosses the Blood–Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts

Indicaxanthin is a bioactive and bioavailable betalain pigment from the Opuntia ficus-indica fruits. In this in vivo study, kinetic measurements showed that indicaxanthin is revealed in the rat brain within 1 h from oral administration of 2 μmol/ kg, an amount compatible with a dietary consumption of cactus pear fruits in humans. A peak (20 ± 2.4 ng of indicaxanthin per whole brain) was measured after 2.5 h; thereafter the molecule disappeared with first order kinetics within 4 h. The potential of indicaxanthin to affect neural activities was in vivo investigated by a microiontophoretic approach. Indicaxanthin, administered in a range between 0.085 ng and 0.34 ng per neuron, dose-dependentl…

ROLE OF NITRIC OXIDE IN THE CONTROL OF MAXIMAL DENTATE GYRUS ACTIVATION BY LAMOTRIGINE IN THE RAT.

Cortical stimulation and reflex excitability of spinal cord neurones in man.

The H reflex technique was used to evaluate the influence exerted by cortical conditioning on the excitability of the alpha-motoneurone pool and on IA interneuronal activity (reciprocal inhibition). In ten subjects at absolute rest electrical and magnetic stimulation of the motor cortex was transcranially applied during flexor carpi radialis H reflex eliciting and in conditions of reciprocal inhibition induced by radial nerve stimulation. The time courses showed that at intensities below motor threshold, electrical brain conditioning induced an increase in the amplitude of the test reflex when the cortical shock was given 4 ms after the test H reflex. On the contrary, reciprocal inhibition …

Through Predictive Personalized Medicine.

Neuroblastoma (NBM) is a deadly form of solid tumor mostly observed in the pediatric age. Although survival rates largely differ depending on host factors and tumor-related features, treatment for clinically aggressive forms of NBM remains challenging. Scientific advances are paving the way to improved and safer therapeutic protocols, and immunotherapy is quickly rising as a promising treatment that is potentially safer and complementary to traditionally adopted surgical procedures, chemotherapy and radiotherapy. Improving therapeutic outcomes requires new approaches to be explored and validated. In-silico predictive models based on analysis of a plethora of data have been proposed by Lomba…

Nitric oxide modulation of the direct pathway in rat basal ganglia circuit

Modulatory effects of nitric oxide-active drugs on the anticonvulsant activity of lamotrigine in an experimental model of partial complex epilepsy in the rat

Abstract Background The effects induced by administering the anticonvulsant lamotrigine, the preferential inhibitor of neuronal nitric oxide synthase 7-nitroindazole and the precursor of NO synthesis L-arginine, alone or in combination, on an experimental model of partial complex seizures (maximal dentate gyrus activation) were studied in urethane anaesthetized rats. The epileptic activity of the dentate gyrus was obtained through the repetitive stimulation of the angular bundle and maximal dentate gyrus activation latency, duration and post-stimulus afterdischarge duration were evaluated. Results Either Lamotrigine (10 mg kg-1) or 7-nitroindazole (75 mg kg-1) i.p. administration had an ant…

Guanosine modulates K+ membrane currents in SH-SY5Y cells: involvement of adenosine receptors

AbstractGuanosine (GUO), widely considered a key signaling mediator, is implicated in the regulation of several cellular processes. While its interaction with neural membranes has been described, GUO still is an orphan neuromodulator. It has been postulated that GUO may eventually interact with potassium channels and adenosine (ADO) receptors (ARs), both particularly important for the control of cellular excitability. Accordingly, here, we investigated the effects of GUO on the bioelectric activity of human neuroblastoma SH-SY5Y cells by whole-cell patch-clamp recordings. We first explored the contribution of voltage-dependent K+ channels and, besides this, the role of ARs in the regulation…

Modulation of Human Motor Cortical Excitability and Plasticity by Opuntia Ficus Indica Fruit Consumption: Evidence from a Preliminary Study through Non-Invasive Brain Stimulation

Indicaxanthin (IX) from Opuntia Ficus Indica (OFI) has been shown to exert numerous biological effects both in vitro and in vivo, such as antioxidant, anti-inflammatory, neuro-modulatory activity in rodent models. Our goal was to investigate the eventual neuro-active role of orally assumed fruits containing high levels of IX at nutritionally-relevant amounts in healthy subjects, exploring cortical excitability and plasticity in the human motor cortex (M1). To this purpose, we applied paired-pulse transcranial magnetic stimulation and anodal transcranial direct current stimulation (a-tDCS) in basal conditions and followed the consumption of yellow cactus pear fruits containing IX or white ca…

Bilateral reciprocal organisation in man: focus on IA interneurone

The H reflex of flexor carpi radialis and radial-induced reciprocal inhibition were recorded in normal subjects during conditioning stimulation of the contralateral median or radial nerves. It was found that stimulation of the contralateral median nerve enhanced the degree of reciprocal inhibition exerted by the radial nerve on the median nerve, while contralateral radial nerve stimulation reduced the reciprocal inhibition exerted by the extensor on the flexor. In two subjects in which a pure extensor H reflex was recorded specular features were observed following contralateral median and radial stimulation. These findings are considered to be the electrophysiological manifestation of contr…

Pregnenolone sulphate enhances spatial orientation and object discrimination in adult male rats: Evidence from a behavioural and electrophysiological study

Abstract Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/kg, s.c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of both spatial orientation–acquisition and object discrimination in a simple and in a complex version of the visual task. Electrophysiological recordings were also performed in vivo , after acute PREGS systemic administration in order to investigate on the neuronal activati…

Can Wii ® remap far into near space?

Background: healthy subjects show in the near space a slight attentional bias toward left (pseudoneglect) that shifts toward right when the task is performed in the far space. This bias moves back again to the left when the subject uses a tool, according to its ability to remap far into near space. On the other hand, when a laser pointer is used to this aim, no significant effects are observed as compared to no-tool condition. This phenomenon has been interpreted as due to the lack of tactile-proprioceptive feedback. Objective: the aim of the present study was to investigate if the use of an interactive tool without tactile- proprioceptive feedback, a three axis accelerometer that works wit…

Reducing Visuospatial Pseudoneglect in Healthy Subjects by Active Video Gaming

Pseudoneglect phenomenon refers to a condition in which healthy subjects tend to perceive the left side of exactly bisected lines as being slightly longer than the right one. However, behavioural data showed that athletes practising an open-skill sport display less pseudoneglect than the general population. Given the fact that so-called exergames (also known as active video games) are platforms designed to fully mimic sport activity, this work intends to investigate whether and how a one-week training period of exergame open-skill sport can determine a similar decrease in pseudoneglect. Fifteen healthy participants (non-athletes) responded to a visuospatial attention task and a control memo…

Nitric oxide and cortico-striato-pallidal motor circuitry: Quantitative EEG analysis of surface and depth recordings

Rats treated with i.p. 7-NI showed a significant increase in cortical higher frequency EEG bands, associated with a corresponding and significant decrease in delta band activity. In the striatum, reduced levels of NO induced an increase in the low frequency band, and a decrease at higher frequencies. Pallidal depth recordings showed modifications to several frequency bands, similar to those found in the cortex. Although 7-NI was administered at increasing doses (from 40 to 70 mg kg–1), it was not possible to demonstrate a relationship between modified band activities and the dose of 7-NI. As suggested indirectly by the quantitative EEG data reported in this study, NO plays a fundamental rol…

Cannabinoid and nitric oxide signaling interplay in the modulation of hippocampal hyperexcitability: study on electrophysiological and behavioral models of temporal lobe epilepsy in the rat

A growing bulk of evidence suggests that cannabinoid system plays a pivotal role in the control of hyperexcitability phenomena. Notwithstanding, the anticonvulsant action of cannabinoids has not been fully addressed, in particular the involvement of potential cellular neuromodulators, for instance nitric oxide. In the current study, we focused on two distinct rat models of temporal lobe epilepsy, the Maximal Dentate Activation and the pilocarpine-induced acute seizures, providing both electrophysiological and behavioral data on cannabinoid and nitrergic system interplay. We evaluated the antiepileptic effects of WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4- morpholinylmethyl) pyrrolo[1,…

N-Valproyl-L-Phenylalanine as new potential antiepileptic drug: Synthesis, characterization and in vitro studies on stability, toxicity and anticonvulsant efficacy

Valproic acid (VPA) is considered first-line drug in treatment of generalized idiopathic seizures such as absence, generalized tonic-clonic and myoclonic seizures. Among major antiepileptic drugs, VPA is also considered effective in childhood epilepsies and infantile spasms. Due to its broad activity, VPA acts as a mood stabilizer in bipolar disorder and it is useful in migraine prophylaxis. Despite its long-standing usage, severe reactions to VPA, such as liver toxicity and teratogenicity, are reported. To circumvent side effects due to structural characteristics of VPA, we synthesized in good yield a new VPA-aminoacid conjugate, the N-valproyl-L-Phenylalanine, and characterized by FT-IR, …

Effects of nitric oxide influence on experimentally-induced hyperexcitability of The hippocampus: in vivo and in vitro comparative electrophysiological study in the rat.

Early handling effect on female rat spatial and non-spatial learning and memory

This study aims at providing an insight into early handling procedures on learning and memory performance in adult female rats. Early handling procedures were started on post-natal day 2 until 21, and consisted in 15 min, daily separations of the dams from their litters. Assessment of declarative memory was carried out in the novel-object recognition task; spatial learning, reference- and working memory were evaluated in the Morris water maze (MWM). Our results indicate that early handling induced an enhancement in: (1) declarative memory, in the object recognition task, both at 1h and 24h intervals; (2) reference memory in the probe test and working memory and behavioral flexibility in the…

EFFECTS OF INDICAXANTHIN ON HUMAN MOTOR CORTICAL EXCITABILITY AND PLASTICITY

The role of nutraceuticals has risen interest in the last decade for complex biological activities exerted on pathophysiological processes such as oxidative stress, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal processes, such as cortical excitability and cortical plasticity are still to be unveiled. Translational studies performed on phytochemicals (PhC) with anti-inflammatory and antioxidant properties could trace the path for the possible modulation of neuronal excitability in humans, phenomena involved in neurodegenerative alterations and cell stress. In this context, Opuntia ficus indica is a mediterranean plant…

Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat

Different studies have been shown a clear anticonvulsant activity exerted by cannabinoids (CB) through the CB1 receptor activation. The purpose of this study was to evaluate, in an in vivo experimental model of temporal lobe epilepsy (maximal dentate gyrus activation - MDA) in the rat, the protective effect of (R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN 55,212-2, CB agonist) alone or in combination with N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB1 antagonist). Pre-treatment with AM251 (1 mg kg-1, 30 min interval) dramatically reduced the signif…

Lamotrigine differently modulates 7-Nitroindazole and L-Arginine influence on Rat Maximal Dentate Gyrus Activation

The effects induced on the maximal dentate gyrus activation (MDA) by administering the anticonvulsant lamotrigine (LTG), the selective inhibitor of neuronal nitric oxide synthase 7-nitroindazole (7-NI) and the precursor of nitric oxide (NO) synthesis L-arginine, alone or in combination, were studied in urethane anaesthetized rats. Either 7-NI or LTG alone administration reduced the number of convulsing animals following angular bundle (AB) stimulation; their combined treatment induced a further increase of the anticonvulsant effect as also demonstrated by the decrease of MDA and afterdischarge (AD) durations in the animals still responding to AB stimulation. On the contrary, the injection o…

Inhibitory effects of N-valproyl-L-tryptophan on high potassium, low calcium and low magnesium-induced CA1 hippocampal epileptiform bursting activity in rat brain slices.

N-valproyl-l-tryptophan (VPA-Tryp), new antiepileptic drug, was tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 or 2 mM) of Valproate (VPA) or VPA-Tryp. Both burst duration and interburst frequency during and after treatment were off-line compared with baseline values. For both parameters, the latency and the length of statistically significant response periods as well as the magnitude of drug-induced responses were calculated. VPA-Tryp evoked fewer and weaker early excitatory effects than VPA on …

Hippocampal hyperexcitability is modulated by microtubule-active agent: evidence from in vivo and in vitro epilepsy models in the rat

The involvement of microtubule dynamics on bioelectric activity of neurons and neurotransmission represents a fascinating target of research in the context of neural excitability. It has been reported that alteration of microtubule cytoskeleton can lead to profound modifications of neural functioning, with a putative impact on hyperexcitability phenomena. Altogether, in the present study we pointed at exploring the outcomes of modulating the degree of microtubule polymerization in two electrophysiological epileptiform activity in the rat hippocampus. To this aim, we used in vivo Maximal Dentate Activation (MDA) and in vitro hippocampal epileptiform bursting activity (HEBA) paradigms to asse…

Nitric oxide/cGMP and Lamotrigine/Vigabatrin effects in a rat model of temporal lobe epilepsy.

Studio del ruolo dell’ossido nitrico nella modulazione dell’attività bioelettrica del complesso strio-pallido-subtalamico del ratto