Serotonin control of central dopaminergic function: focus on in vivo microdialysis studies

In this review, the functional interactions between serotonin (5-HT) and dopamine (DA) neuronal systems are discussed with the focus on microdialysis studies in the rodent brain (mainly rats). 5-HT by itself is involved both directly and indirectly via actions on complex neuronal circuitry, in the regulation of DA release through multiple 5-HT receptors, playing a critical role in the development of normal and abnormal behaviours. Recent evidence suggests that dysfunction of dopaminergic and serotoninergic neurotransmitter systems contributes to various disorders including depression, schizophrenia, Parkinson's disease and drug abuse. Here we summarize recent neurochemical works that have e…

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…

Enhanced tonic GABAA inhibition in typical absence epilepsy

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired γ-aminobutyric acid (GABA)-ergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent 'tonic' inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT-1 in the genetic models tested, and GAT-1 is crucial in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best character…

The neurobiological bases for the pharmacotherapy of nicotine addiction.

Nicotine, the major psychoactive agent present in tobacco, acts as a potent addictive drug both in humans and laboratory animals, whose locomotor activity is also stimulated. A large body of evidence indicates that the locomotor activation and the reinforcing effects of nicotine may be related to its stimulatory effects on the mesolimbic dopaminergic function. Thus, it is now well established that nicotine can increase in vivo DA outflow in the nucleus accumbens and the corpus striatum. The stimulatory effect of nicotine on DA release most probably results from its ability to excite the neuronal firing rate and to increase the bursting activity of DA neurons in the substantia nigra pars com…

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

Nitric oxide modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders.

Several recent studies have emphasized a crucial role for the nitrergic system in movement control and the pathophysiology of the basal ganglia (BG). These observations are supported by anatomical evidence demonstrating the presence of nitric oxide synthase (NOS) in all the basal ganglia nuclei. In fact, nitrergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high expression of nitric oxide (NO)-producing neurons, with the striatum having the greatest number, together with important NO afferent input. In this pape…

A rapid and quantitative technique to study striatal dopaminergic neurodegeneration by in vivo reverse microdialysis in rats

Impact of serotonin 2C receptor null mutation on physiology and behavior associated with nigrostriatal dopamine pathway function.

The impact of serotonergic neurotransmission on brain dopaminergic pathways has substantial relevance to many neuropsychiatric disorders. A particularly prominent role has been ascribed to the inhibitory effects of serotonin 2C receptor (5-HT2CR) activation on physiology and behavior mediated by the mesolimbic dopaminergic pathway, particularly in the terminal region of the nucleus accumbens. The influence of this receptor subtype on functions mediated by the nigrostriatal dopaminergic pathway is less clear. Here we report that a null mutation eliminating expression of 5-HT2CRs produces marked alterations in the activity and functional output of this pathway. 5-HT2CR mutant mice displayed i…

Selective stimulation of serotonin2c receptors blocks the enhancement of striatal accumbal dopamine release by nicotine administration

Lateral Habenula 5-HT2C Receptor Function Is Altered by Acute and Chronic Nicotine Exposures

Serotonin (5-HT) is important in some nicotine actions in the CNS. Among all the 5-HT receptors (5-HTRs), the 5-HT2CR has emerged as a promising drug target for smoking cessation. The 5-HT2CRs within the lateral habenula (LHb) may be crucial for nicotine addiction. Here we showed that after acute nicotine tartrate (2 mg/kg, i.p.) exposure, the 5-HT2CR agonist Ro 60-0175 (5–640 µg/kg, i.v.) increased the electrical activity of 42% of the LHb recorded neurons in vivo in rats. Conversely, after chronic nicotine treatment (6 mg/kg/day, i.p., for 14 days), Ro 60-0175 was incapable of affecting the LHb neuronal discharge. Moreover, acute nicotine exposure increased the 5-HT2CR-immunoreactive (IR)…

Central Serotonin2C Receptor: From Physiology to Pathology

Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central nervous system (CNS), an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a number of cognitive and behavioural functions. Although 5-HT is synthesized by a small group of neurons within the raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic projections. Furthermore, the importance of 5-HT modulation and the fine-tuning of its action is underlined by the large number of 5-HT binding sites found in the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been identified. This review was undertaken to summarize the work that has…

Serotonin 5-HT2C Receptor and Dopamine Function in Depression

Effects of Substantia Nigra pars compacta lesion on the behavioral sequencing in the 6-OHDA model of Parkinson’s disease

The basal ganglia circuitry plays a crucial role in the sequential organization of behavior. Here we studied the behavioral structure of the animals after 21 days of 6-OHDA-induced lesion of the dopaminergic nigrostriatal system. Frequencies and durations of individual components of the behavioral repertoire were calculated; moreover, whether a temporal organization of the activity was present, it was investigated by using T-pattern analysis, a multivariate approach able to detect the real-time sequential organization of behavior. Six sham-depleted and six rats with unilateral 6−OHDA-lesion of the Substantia Nigra pars compacta were used. As to quantitative evaluations, the comparison betwe…

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo.

Although several studies have emphasized a crucial role for the serotonergic system in the control of hippocampal excitability, the role of serotonin (5-HT) and its receptors in normal and pathologic conditions, such as temporal lobe epilepsy (TLE), is still unclear. The present study was therefore designed firstly to investigate the acute effect of 8-OH-DPAT, a mixed 5-HT1A/7 receptor agonist, at a high dose (1 mg/kg, i.p.) known to have antiepileptic properties, in a model of acute partial epilepsy in rats. For this purpose, a maximal dentate activation (MDA) protocol was used to measure electrographic seizure onset and duration. In addition, the effect of 8-OH-DPAT on in vivo dentate gyr…

Nitric Oxide Modulation of the Dopaminergic Nigrostriatal System: Focus on Nicotine Action

Nitric oxide (NO) signalling plays an important role in the integration of information processed by the basal ganglia nuclei. Accordingly, considerable evidence has emerged indicating a role for NO in pathophysiological conditions such as Parkinson’s disease (PD), schizophrenia and drug addiction. To further investigate the NO modulation of dopaminergic function in the basal ganglia circuitry, in this study we used in vivo electrophysiology and microdialysis in freely-moving rats. Pharmacological manipulation of the NO system did not cause any significant changes either in the basal firing rate and bursting activity of the dopamine (DA) neurons in the substantia nigra pars compacta (SNc) or…

Unilateral Nigral Lesion Induces Dramatic Bilateral Modification In Rat Brain Monoamine Levels: A Neurochemical Study.

ACETYLSALYCILIC ACID (ASA) PROTECTS AGAINST NEURONAL DAMAGE INDUCED BY 1-METHYL-4-PHENYLPYRIDINIUM IODIDE (MPP+) IN RAT STRIATUM: AN IN VIVO MICRODIALYSIS STUDY

Biochemical evidence that the atypical antipsychotic drugs clozapine and risperidone block 5-HT(2C) receptors in vivo.

Clozapine and risperidone are two atypical antipsychotic drugs which bind, among other receptors, to 5-HT(2C) receptor subtypes. They inhibit the basal inositol phosphate production in mammalian cells expressing rat or human 5-HT(2C) receptors. This biochemical effect is indicative of inverse agonist activity at these receptors. There is evidence that 5-HT(2C) receptors are involved in the control of the activity of central dopaminergic system. Therefore, the effects of clozapine (5 mg/kg ip), risperidone (0.08 mg/kg ip) and of the typical antipsychotic haloperidol (0.1 mg/kg ip) were studied on the extracellular concentration of dopamine (DA) in the nucleus accumbens of chloral hydrate-ane…

Structural analyses in the study of behavior : From rodents to non-human primates

Ajuts: J-BL's research was funded by Natural Sciences and Engineering Research Council of Canada (NSERC, Discovery Grant #: 2015-06034 to J-BL). MC, SA, and GC's research was funded by a grant from the University of Palermo, Italy. The term " structure " indicates a set of components that, in relation to each other, shape an organic complex. Such a complex takes on essential connotations of functionally unitary entity resulting from the mutual relationships of its constituent elements. In a broader sense, we can use the word " structure " to define the set of relationships among the elements of an emergent system that is not determined by the mere algebraic sum of these elements, but by the…

Involvement of Nitric Oxide in Nigrostriatal Dopaminergic System Degeneration : A Neurochemical Study.

The present study was undertaken to explore the involvement of nitric oxide (NO) in the 6-hydroxydopamine (6-OHDA) experimental model of Parkinson's disease (PD) in rats. The effect of pharmacological manipulation of the NO system was evaluated on striatal dopamine (DA) level decrease produced by the toxin. 7-nitroindazole (7-NI, 50 mg/kg i.p.; n= 5) pretreatment significantly restored the striatal DA contents. Conversely, 40 mg/kg i.p. of molsidomine (MOL, n= 5), an NO donor, significantly worsened the neurodegeneration (n= 5) and completely counteracted the neuroprotective effect of 7-NI (n= 5). Thus, a crucial role for NO in 6-OHDA induced neurodegeneration is suggested together with a p…

ROLE OF CENTRAL 5-HT2C RECEPTOR IN THE CONTROLL OF BASAL GANGLIA FUNCTIONS

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 …

Nicotine modulation of the lateral habenula/ventral tegmental area circuit dynamics: An electrophysiological study in rats

Abstract Nicotine, the addictive component of tobacco, has bivalent rewarding and aversive properties. Recently, the lateral habenula (LHb), a structure that controls ventral tegmental area (VTA) dopamine (DA) function, has attracted attention as it is potentially involved in the aversive properties of drugs of abuse. Hitherto, the LHb-modulation of nicotine-induced VTA neuronal activity in vivo is unknown. Using standard single-extracellular recording in anesthetized rats, we observed that intravenous administration of nicotine hydrogen tartrate (25–800 μg/kg i.v.) caused a dose-dependent increase in the basal firing rate of the LHb neurons of nicotine-naive rats. This effect underwent com…

mGluR control of interneuron output regulates feedforward tonic GABAA inhibition in the visual thalamus

Metabotropic glutamate receptors (mGluRs) play a crucial role in regulation of phasic inhibition within the visual thalamus. Here we demonstrate that mGluR-dependent modulation of interneuron GABA release results in dynamic changes in extrasynaptic GABAA receptor (eGABAAR)-dependent tonic inhibition in thalamocortical (TC) neurons of the rat dorsal lateral geniculate nucleus (dLGN). Application of the group I selective mGluR agonist dihydroxyphenylglycine produces a concentration-dependent enhancement of both IPSC frequency and tonic GABAA current (IGABAtonic) that is due to activation of both mGluR1a and mGluR5 subtypes. In contrast, group II/III mGluR activation decreases both IPSC freque…

Role of nitric oxide on the conrol of the dopaminergic Nigrostriatal system: a combined electrophysiological And dialysis analysis in rats

Electrophysiological and Neurochemical In Vivo Studies on Serotonin 5-HT 2C Control of Central Dopaminergic Function

Serotonin–dopamine interaction: electrophysiological evidence

In this review, the most relevant data regarding serotonin (5-hydroxytryptamine, 5-HT)/dopamine (DA) interaction in the brain, as studied by both in vivo and in vitro electrophysiological methods, are reported and discussed. The bulk of neuroanatomical data available clearly indicate that DA-containing neurons in the brain receive a prominent innervation from 5-HT originating in the raphe nuclei of the brainstem. Furthermore, this modulation seems to be reciprocal; DA neurons innervate the raphe nuclei and exert a tonic excitatory effect on them. Compelling electrophysiological data show that 5-HT can exert complex effects on the electrical activity of midbrain DA neurons mediated by the va…

MUSCARINIC MODULATION OF THE ACTIVITY OF THE SUBSTANTIA NIGRA PARS COMPACTA NEURONS IN RATS: ROLE OF THE TEGMENTAL PEDUNCULOPONTINE NUCLEUS

The unilateral nigral lesion induces dramatic bilateral modification on rat brain monoamine neurochemistry

6-Hydroxydopamine (6-OHDA) is a neurotoxic compound commonly used to induce dopamine (DA) depletion in the nigrostriatal system, mimicking Parkinson's disease (PD) in animals. The aim of the present study was to evaluate the 7-day effect of unilateral nigral lesion on rat brain monoamine neurochemistry. Five brain regions were examined: the brain stem, cerebellum, hippocampus, striatum, and cortex. 6-OHDA-unilateral lesion dramatically modified DA, serotonin (5-HT) and their metabolites contents in both sides of the different brain nuclei. Furthermore, unilateral 6-OHDA lesion reduced DA and 5-HT contents and produced a robust inversion of their turnover in the nonlesioned side compared to …

7-Nitroindazole protects striatal neurons against MPP+ -induced degeneration.

The neuropathological hallmark of Parkinson's disease (PD) is the selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). In this study, using a microdialysis technique, we investigated whether an inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitrindazole (7-NI), could protect against DAergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP+) in freely moving rats. Experiments were performed over 2 days in three groups of rats: (a) nonlesioned, (b) MPP+-lesioned, and (c) 7-NI pretreated MPP+-lesioned rats. On day 1, control rats were perfused with an artificial CSF, while 1 mM MPP+ was infused into t…

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

Serotonin–dopamine interaction: an overview

Central serotonergic and dopaminergic systems play a critical role in the regulation of normal and abnormal behaviours. Moreover, recent evidence suggests that the dysfunction of dopamine (DA) and serotonin (5-hydroxytriptamine, 5-HT) neurotransmission might underlie the pathophysiology of neuropsychiatric disorders, including depression, schizophrenia, attention deficit hyperactivity disorders, drug abuse, Gilles de la Tourette's syndrome and Parkinson's disease.

T-patterns in the study of movement and behavioral disorders

Aim of the present review is to offer an outline of the application of T-pattern analysis (TPA) in the study of neurological disorders characterized by anomalies of movement and, more in general, of behavior. TPA is a multivariate technique to detect real time patterns of behavior on the basis of statistically significant constraints among the events in sequence. TPA is particularly suitable to analyse the structure of behavior. The application of TPA to study movement and behavioral disorders is able to offer, with a high level of detail, hidden characteristics of behavior otherwise impossible to detect. For its intrinsic features, TPA is completely different not only from quantitative eva…

7-nitroindazole protects striatal dopaminergic neurons against MPP+-induced degeneration: an in vivo microdialysis study.

The neuropathological hallmark of Parkinson's disease (PD) is the selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). In this study, using a microdialysis technique, we investigated whether an inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitrindazole (7-NI), could protect against DAergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP(+)) in freely moving rats. Experiments were performed over 2 days in three groups of rats: (a) nonlesioned, (b) MPP(+)-lesioned, and (c) 7-NI pretreated MPP(+)-lesioned rats. On day 1, control rats were perfused with an artificial CSF, while 1 mM MPP(+) was infuse…

Acute and chronic nicotine exposures differentially affect central serotonin 2A receptor function : focus on the lateral habenula

Nicotine addiction is a serious public health problem causing millions of deaths worldwide. Serotonin (5-hydroxytryptamine

Serotonin-dopamine interaction: electrophysiological evidence.

In this review, the most relevant data regarding serotonin (5-hydroxytryptamine, 5-HT)/dopamine (DA) interaction in the brain, as studied by both in vivo and in vitro electrophysiological methods, are reported and discussed. The bulk of neuroanatomical data available clearly indicate that DA-containing neurons in the brain receive a prominent innervation from 5-HT originating in the raphe nuclei of the brainstem. Furthermore, this modulation seems to be reciprocal; DA neurons innervate the raphe nuclei and exert a tonic excitatory effect on them. Compelling electrophysiological data show that 5-HT can exert complex effects on the electrical activity of midbrain DA neurons mediated by the va…

Involvement of nitric oxide in the nigrostriatal dopaminergic system degeneration: a study on the 6-OHDA model of Parkinson's disease.

Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

INFLAMMATION IN PARKINSON'S DISEASE

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, …

Role(s) of the 5-HT2C receptor in the development of maximal dentate activation in the hippocampus of anesthetized rats.

Aims: Substantial evidence indicates that 5-HT2C receptors are involved in the control of neuronal network excitability and in seizure pathophysiology. Here, we have addressed the relatively unexplored relationship between temporal lobe epilepsy (TLE), the most frequent type of intractable epilepsy, and 5-HT2CRs. Methods: In this study, we investigated this issue using a model of partial complex (limbic) seizures in urethane-anesthetized rat, based on the phenomenon of maximal dentate activation (MDA) using 5-HT2C compounds, electrophysiology, immunohistochemistry, and western blotting techniques. Results: The 5-HT2C agonists mCPP (1 mg/kg, i.p) and lorcaserin (3 mg/kg, i.p), but not RO60-0…

Effects of chronic nicotine on the temporal structure of anxiety-related behavior in rats tested in hole-board.

Abstract The present study aimed to assess the behavioral effects of chronic treatments of different doses of nicotine by using both quantitative and multivariate T-pattern analysis (TPA), which can reveal hidden behavioral structures, in Sprague-Dawley rats tested in the hole-board apparatus. To this purpose, nicotine ditartrate was administered at the doses of 0.1, 0.5 and 1 mg/kg i.p., three times per day, for 14 consecutive days. As to quantitative evaluations, we observed significant reductions in the mean durations and mean frequencies of walking, climbing, immobile-sniffing and rearing in comparison to control. A significant reduction of edge-sniff and head-dip mean frequencies was a…

Acute Nicotine Induces Anxiety and Disrupts Temporal Pattern Organization of Rat Exploratory Behavior in Hole-Board: A Potential Role for the Lateral Habenula

Nicotine is one of the most addictive drugs of abuse. Tobacco smoking is a major cause of many health problems, and is the first preventable cause of death worldwide. Several findings show that nicotine exerts significant aversive as well as the well-known rewarding motivational effects. Less certain is the anatomical substrate that mediates or enables nicotine aversion. Here, we show that acute nicotine induces anxiogenic-like effects in rats at the doses investigated (0.1, 0.5, and 1.0 mg/kg, i.p.), as measured by the hole-board apparatus and manifested in behaviors such as decreased rearing and head-dipping and increased grooming. No changes in locomotor behavior were observed at any of …

Serotonin and Dopamine Interaction: An Overview

Central serotonergic and dopaminergic systems play a critical role in the regulation of normal and abnormal behaviours. Moreover, recent evidence suggests that the dysfunction of dopamine (DA) and serotonin (5-hydroxytriptamine, 5-HT) neurotransmission might underlie the pathophysiology of neuropsychiatric disorders, including depression, schizophrenia, attention deficit hyperactivity disorders, drug abuse, Gilles de la Tourette's syndrome and Parkinson's disease.

Hsp60 response in experimental and human temporal lobe epilepsy due to hyppocampal sclerosis

Hsp60 is widely distributed in the brain, and its alteration has been involved in different neurological disorders. Epilepsy is considered one of the most common neurological disorders and typically involves the hippocampal formation. Compelling evidence describes a role of mitochondria, oxidative stress and both innate and adaptive immunity during epileptogenesis in temporal lobe epilepsy due to hyppocampal sclerosis (TLE-HS). Here, we investigate the Hsp60 involvement in experimental and human epilepsy. Firstly, expression and distribution of Hsp60 in epileptic hippocampi of a rat model of temporal lobe epilepsy (TLE), based on the phenomenon of maximal dentate gyrus activation (MDA), usi…

Nitric oxide: Implications for the etiology & treatment of central nervous system disorders

CCK-8S systemic administration blocks the 7-nitroindazole-induced effects on the EEG of striatum and globus pallidus: a FFT analysis in the rat

Background: Nitric oxide (NO) and cholecystokinin (CCK) are involved in the modulation of several neurotransmitter systems in the basal ganglia, and a functional interaction between their modulatory effects could be hypothesised. Materials and Methods: We studied the effects exerted by the administration of 7-nitroindazole (7-NI) (50 mg kg-1 i.p.), a selective inhibitor of neuronal NO synthase, on the depth EEG activity of the striatum and of the globus pallidus in both not pre-treated and sulphated CCK octapeptide (CCK- 8S)-treated (100 nM kg-1 i.p.) rats. Striatal and pallidal depth EEG power spectra were examined by means of a Fast Fourier Transform analysis. Results: Striatal depth reco…

Author Correction: The FAAH inhibitor URB597 suppresses hippocampal maximal dentate afterdischarges and restores seizure-induced impairment of short and long-term synaptic plasticity

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

The Life Cycle of the Dopaminergic Neurons in the Substantia Nigra

Intake of Tomato-Enriched Diet Protects from 6-Hydroxydopamine-Induced Degeneration of Rat Nigral Dopaminergic Neurons

There is extensive evidence that oxidative damage of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc) may contribute to the pathogenesis of Parkinson’s disease (PD). We evaluated the potential neuroprotective effect of diets enriched with wild-type Red Setter (RS) tomato or transgenic High Carotene (HC) tomato, rich in β-carotene, obtained by the activation of lycopene β-cyclase (tlcy-b), in an animal model of PD. Male Fischer 344 rats were fed for 14 days with standard AltrominMT diet, 5% RS- or 5% HC-enriched diet. Seven days after the beginning of this diet regimen, the rats were lesioned by 6-hydroxydopamine (6-OHDA) injected into the left SNc. After further …

Combining Quantitative and Qualitative Data in the Study of Feeding Behavior in Male Wistar Rats

The first step in a behavioral study is represented by the organization of a suitable ethogram, that is, a formal description of individual components of the behavior. Then, each component of such a behavioral repertoire can be quantified (e.g., how many times it occurs, its duration, percent distribution, latency, etc.). However, it is our contention that the possibility to describe the behavior of a living being by means of hundreds or even thousands of numbers concerning isolated components, disjointed from the comprehensive behavioral architecture, does not imply the possibility to use those numbers to reconstruct the meaning of behavior. Such a level of comprehension requires a qualita…

The effect of cannabinoid receptor agonist WIN 55,212-2 on anxiety-like behavior and locomotion in a genetic model of absence seizures in the elevated plus-maze.

GAERS and NEC rats were treated with cannabinoid 1/2 receptor agonist WIN 55,212-2 2 mg/kg and tested on the Elevated Plus-Maze

Neuroprotection in Parkinson's Disease: a Realistic Goal?

The current issue of CNS Neuroscience & Therapeutics contains an interesting review by Kinecses and Vecsei [1] on the progress in our knowledge related to the pathophysiological mechanisms of Parkinson's disease (PD) and on the development of putative neuroprotective molecules. Since the seminal discovery by Oleh Hornykiewicz that degeneration of DA neurons within the substantia nigra pars compacta (SNc) and the consequential dopamine depletion in the striatum was the cause of neurological symptoms in PD [2], thousands of reviews have been written on the subject, some of them possibly superfluous. Nevertheless, we found this last work enjoyable in terms of readability and in the way the aut…

Modifications induced on rat exploratory behavior by acoustic stimulation: a multivariate analysis

Effects of scopolamine on dopamine neurons in the substantia nigra : role of the pedunculopontine tegmental nucleus

Previous neurochemical and behavioral studies suggest that muscarinic receptor antagonism has an excitatory effect on the nigrostriatal dopamine (DA) system. Using in vivo extracellular single unit recording, this study examined whether blockade of the muscarinic receptor by scopolamine alters the firing properties of DA neurons in the substantia nigra (SN). Scopolamine was administered either systemically or locally to DA neurons using microiontophoresis. Surprisingly, scopolamine did not cause any significant change in either the firing rate or pattern of the spontaneously active DA neurons. However, systemic injection of scopolamine significantly increased the number of active DA neurons…

Editorial [ Neurodegenerative Disorders: From Molecules to Man (Part 2) Guest Editors: Giuseppe Di Giovanni, Vincenzo Di Matteo and Ennio Esposito ]

NEURODEGENERATIVE DISORDERS: FROM MOLECULES TO MAN

Extrasynaptic GABAA receptor gain-of-function in absence epilepsy: GHB and thip pharmacological models

Preferential Modulation of the GABAergic vs. Dopaminergic Function in the Substantia Nigra by 5-HT2C Receptor

Serotonin (5-HT) is intimately involved in the modulation of the basal ganglia circuitry and in its pathologies. The 5-HT pivotal role is supported by anatomical evidence demonstrating a large serotonergic innervation throughout the basal ganglia, with the highest concentration of this indole in the substantia nigra (SN). Among all the 5-HT receptors present in the SN, the 5-HT2C receptor subtype seems to be one of the principal receptors through which 5-HT exerts its function. In this chapter, we present in vivo electrophysiology and microdialysis evidence showing that the selective activation of 5-HT2C receptors does not affect dopaminergic function whereas it has a profound impact on GAB…

Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis

Cholinergic and monoaminergic modulation of tonic GABAA inhibition in the rat dorsal lateral geniculate nucleus

ROLE OF CENTRAL 5-HT2C RECEPTOR IN THE CONTROLL OF BASAL GANGLIA FUNCTIONS.

In Vivo Microdialysis in Parkinson’s Research

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopamine (DA) neurons in the nigrostriatal system, which in turn produces profound neurochemical changes within the basal ganglia, representing the neural substrate for parkinsonian motor symptoms. The pathogenesis of the disease is still not completely understood, but environmental and genetic factors are thought to play important roles. Research into the pathogenesis and the development of new therapeutic intervention strategies that will slow or stop the progression of the disease in human has rapidly advanced by the use of neurotoxins that specifically target DA ne…

Critical role of nitric oxide on nicotine-induced hyperactivation of dopaminergic nigrostriatal system: electrophysiological and neurochemical evidence in rats

Nicotine, the main psychoactive ingredient in tobacco, stimulates dopamine (DA) function, increasing DA neuronal activity and DA release. DA is involved in both motor control and in the rewarding and reinforcing effects of nicotine; however, the complete understanding of its molecular mechanisms is yet to be attained. Substantial evidence indicates that the reinforcing properties of drugs of abuse, including nicotine, can be affected by the nitric oxide (NO) system, which may act by modulating central dopaminergic function. In this study, using single cell recordings in vivo coupled with microiontophoresis and microdialysis in freely moving animals, the role of NO signaling on the hyperacti…

The FAAH inhibitor URB597 suppresses hippocampal maximal dentate afterdischarges and restores seizure-induced impairment of short and long-term synaptic plasticity

Synthetic cannabinoids and phytocannabinoids have been shown to suppress seizures both in humans and experimental models of epilepsy. However, they generally have a detrimental effect on memory and memory-related processes. Here we compared the effect of the inhibition of the endocannabinoid (eCB) degradation versus synthetic CB agonist on limbic seizures induced by maximal dentate activation (MDA) acute kindling. Moreover, we investigated the dentate gyrus (DG) granule cell reactivity and synaptic plasticity in naïve and in MDA-kindled anaesthetised rats. We found that both the fatty acid amide hydrolase (FAAH) inhibitor URB597 and the synthetic cannabinoid agonist WIN55,212-2 displayed AM…

The Pivotal Role of Nitric Oxide in 6-OHDA-induced Dopaminergic Neurotoxicity: Neurochemical Evidences in Rats

Critical role of Nitric Oxide on Nicotine-Induced Hyperactivation of Dopaminergic Nigrostriatal System: Electrophysiological and Neurochemical evidence in Rats

Nicotine, the main psychoactive ingredient in tobacco, stimulates dopamine (DA) function, increasing DA neuronal activity and DA release. DA is involved in both motor control and in the rewarding and reinforcing effects of nicotine; however, the complete understanding of its molecular mechanisms is yet to be attained. Substantial evidence indicates that the reinforcing properties of drugs of abuse, including nicotine, can be affected by the nitric oxide (NO) system, which may act by modulating central dopaminergic function. In this study, using single cell recordings in vivo coupled with microiontophoresis and microdialysis in freely moving animals, the role of NO signaling on the hyperacti…

THE SUBSTANTIA NIGRA DOPAMINERGIC NEURONS

Dopamine Interaction with other Neurotransmitter Systems: Relevance in the Pathophysiology and Treatment of CNS Disorders

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the d…

Death in the substantia nigra: a motor tragedy

It is well known that the death of dopaminergic neurons of the substantia nigra pars compacta (SNc) is the pathological hallmark of Parkinson's disease (PD), the second most common and disabling condition in the expanding elderly population. Nevertheless, the intracellular cascade of events leading to dopamine cell death is still unknown and, consequently, treatment is largely symptomatic rather than preventive. Moreover, the mechanisms whereby nigral dopaminergic neurons may degenerate still remain controversial. Hitherto, several data have shown that the earlier cellular disturbances occurring in dopaminergic neurons include oxidative stress, excitotoxicity, inflammation, mitochondrial dy…

Essential thalamic contribution to slow waves of natural sleep

Slow waves represent one of the prominent EEG signatures of non-rapid eye movement (non-REM) sleep and are thought to play an important role in the cellular and network plasticity that occurs during this behavioral state. These slow waves of natural sleep are currently considered to be exclusively generated by intrinsic and synaptic mechanisms within neocortical territories, although a role for the thalamus in this key physiological rhythm has been suggested but never demonstrated. Combining neuronal ensemble recordings, microdialysis, and optogenetics, here we show that the block of the thalamic output to the neocortex markedly (up to 50%) decreases the frequency of slow waves recorded dur…

Application of T-pattern analysis in the study of the organization of behavior

CRUCIAL ROLE OF THE 5-HT2C RECEPTOR IN REGULATING THE ACTIVITY OF THE SUBSTANTIA NIGRA PARS RETICULATA NEURONS: AN ELECTROPHYSIOLOGICAL STUDY IN RATS

Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats

Abstract Endocannabinoids (eCBs) and serotonin (5-HT) play a neuromodulatory role in the central nervous system. Both eCBs and 5-HT regulate neuronal excitability and their pharmacological potentiation has been shown to control seizures in pre-clinical and human studies. Compelling evidence indicates that eCB and 5-HT systems interact to modulate several physiological and pathological brain functions, such as food intake, pain, drug addiction, depression, and anxiety. Nevertheless, there is no evidence of an eCB/5-HT interaction in experimental and human epilepsies, including status epilepticus (SE). Here, we performed video-EEG recording in behaving rats treated with the pro-convulsant age…

Serotonin Involvement in the Basal Ganglia Pathophysiology: Could the 5-HT2C Receptor be a New Target for Therapeutic Strategies?.

The basal ganglia are a highly interconnected group of subcortical nuclei in the vertebrate brain that play a critical role not only in the control of movements but also in some cognitive and behavioral functions. Several recent studies have emphasized that serotonergic pathways in the central nervous system (CNS) are intimately involved in the modulation of the basal ganglia and in the pathophysiology of human involuntary movement disorders. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of the basal ganglia. In fact, serotonergic terminals have been reported to make synaptic contacts with dopamine (DA)-containing neurons and gamma-amin…

Serotonin modulation of the basal ganglia circuitry : therapeutic implication for Parkinson’s disease and other motor disorders

Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the d…

Effects of Different Anxiety Levels on the Behavioral Patternings Investigated through T-pattern Analysis in Wistar Rats Tested in the Hole-Board Apparatus

The Hole-Board is an ethologically based tool for investigating the anxiety-related behavior of rats following manipulation of the central anxiety level. The present paper aims to assess behavioral patterning following pharmacological manipulation of emotional assets in Wistar rats tested in this experimental apparatus. For this purpose, the behavior of three groups of rats injected with saline, diazepam or FG7142 was evaluated using conventional quantitative and multivariate Tpattern analyses. The results demonstrate that quantitative analyses of individual components of the behavior, disjointed from the comprehensive behavioral structure, are of narrow utility in the understanding of the …

Selective Activation of Serotonin2C Receptors Stimulates GABA-ergic Function in the Rat Substantia Nigra Pars Reticulata: A Combined in Vivo Electrophysiological and Neurochemical Study.

In vivo electrophysiology and microdialysis were used to investigate the physiological role of 5-HT2C receptors in the control of substantia nigra pars reticulata (SNr) function. Extracellular single-unit recordings were performed from putative GABA-containing neurons in the SNr of anesthetized rats, and local GABA release was studied by in vivo microdialysis in the SNr of awake freely-moving rats. Systemic administration of the selective 5-HT2C receptor agonist (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 (RO 60-0175) caused a dose-dependent excitation of about 30% of the SNr neurons recorded. However, the remaining neurons were either inhibited or unaffected by systemi…

The impact of chronic daily nicotine exposure and its overnight withdrawal on the structure of anxiety-related behaviors in rats: Role of the lateral habenula.

Tobacco smoking is a serious health problem worldwide and a leading cause of mortality. Nicotine, the addictive component of tobacco, affects a range of emotional responses, including anxiety-related behaviors. Although perceived by smokers to be anxiolytic, evidence suggests that smoking increases anxiety and that mood fluctuates with nicotine intake. Thus, nicotine addiction may depend on easing the psychobiological distress caused by its abuse. The lateral habenula (LHb) has been implicated as a neural substrate for acute nicotine-induced anxiety, but its role in anxiety-like behaviors associated with chronic nicotine exposure has not been explored. Here, we assessed the effect of chroni…

Preferential modulation of the gabaergic vs. dopaminergic function in the substantia nigra by 5-TH2C receptor signaling: electrophysiological and neurochemical evidence

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…

Hsp60 response in experimental and human temporal lobe epilepsy

The mitochondrial chaperonin Hsp60 is a ubiquitous molecule with multiple roles, constitutively expressed and inducible by oxidative stress. In the brain, Hsp60 is widely distributed and has been implicated in neurological disorders, including epilepsy. A role for mitochondria and oxidative stress has been proposed in epileptogenesis of temporal lobe epilepsy (TLE). Here, we investigated the involvement of Hsp60 in TLE using animal and human samples. Hsp60 immunoreactivity in the hippocampus, measured by Western blotting and immunohistochemistry, was increased in a rat model of TLE. Hsp60 was also increased in the hippocampal dentate gyrus neurons somata and neuropil and hippocampus proper …

Different Representation Procedures Originated from Multivariate Temporal Pattern Analysis of the Behavioral Response to Pain in Wistar Rats Tested in a Hot-Plate under Morphine

Temporal pattern analysis is an advanced multivariate technique able to investigate the structure of behavior by unveiling the existence of statistically significant constraints among the interval length separating events in sequence. If on the one hand, such an approach allows investigating the behavioral response to pain in its most intimate and inner features, on the other hand, due to the meaning of the studies on pain, it is of relevant importance that the results utilize intuitive and easily comprehensible ways of representation. The aim of this paper is to show various procedures useful to represent the results originating from the multivariate T-pattern analysis of the behavioral re…

Serotonin control of central dopaminergic function: focus on in vivo microdialysis studies

In this review, the functional interactions between serotonin (5-HT) and dopamine (DA) neuronal systems are discussed with the focus on microdialysis studies in the rodent brain (mainly rats). 5-HT by itself is involved both directly and indirectly via actions on complex neuronal circuitry, in the regulation of DA release through multiple 5-HT receptors, playing a critical role in the development of normal and abnormal behaviours. Recent evidence suggests that dysfunction of dopaminergic and serotoninergic neurotransmitter systems contributes to various disorders including depression, schizophrenia, Parkinson's disease and drug abuse. Here we summarize recent neurochemical works that have e…

Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study.

The effect of aspirin on dopaminergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP(+)) and 6-hydroxydopamine (6-OHDA) was studied in rats, using microdialysis. Rat striata were perfused with 1 mM MPP(+) or 6-OHDA for 10 min, causing peak levels of dopamine (DA) in the dialytic fluid, after 40 min. After 24 h, 1 mM MPP(+) was perfused again for 10 min and DA levels measured in the dialytic fluid, as an index of neuronal cell integrity. Pretreatment with Aspidol (lysine acetylsalicylate), 180 mg/kg i.p., 1 h before MPP(+) or 6-OHDA perfusion, did not modify DA extracellular output, on day 1, but restored MPP(+)-induced DA release on day 2, indicating …

Electrophysiological and Neurochemical Characterization of 7-Nitroindazole and Molsidomine Acute and Sub-Chronic Administration Effects in the Dopaminergic Nigrostrial System in Rats

Nitric oxide (NO) plays an important role in the integration of information processed by the basal ganglia nuclei. Accordingly, considerable evidence has emerged indicating a role for NO in pathophysiological conditions such as Parkinson’s disease (PD) and other neurodegenerative disorders. Despite these recent advances, the nitrergic modulation of the dopamine (DA) nigrostriatal system is still unclear. In order to fill this gap, in this study we used in vivo electrophysiology and ex vivo neurochemical analysis to further investigate the effect of NO signaling in rat substantia nigra pars compacta (SNc) and the striatum. Acute and subchronic (4 days) pharmacological manipulation of the NO …

Lorcaserin bidirectionally regulates dopaminergic function site-dependently and disrupts dopamine brain area correlations in rats

Abstract Lorcaserin, which is a selective agonist of serotonin2C receptors (5-HT2CRs), is a new FDA-approved anti-obesity drug that has also shown therapeutic promise in other brain disorders, such as addiction and epilepsy. The modulation of dopaminergic function might be critical in the therapeutic effect of lorcaserin, but its exact effect is unknown. Here, we studied the effect of the peripheral administration of lorcaserin on the ventral tegmental area (VTA), the substantia nigra pars compacta (SNc) dopaminergic neural activity, dopamine (DA) dialysis levels in the nucleus accumbens and striatum and on DA tissue levels in 29 different rat brain regions. Lorcaserin (5–640 μg/kg, i.v.) m…

Electrophysiological and neurochemical characterization of 7-nitroindazole and molsidomine acute and sub-chronic administration effects in the dopaminergic nigrostriatal system in rats

Nicotine, the main psychoactive ingredient in tobacco, stimulates dopamine (DA) function, increasing DA neuronal activity and DA release. DA is involved in both motor control and in the rewarding and reinforcing effects of nicotine; however, the complete understanding of its molecular mechanisms is yet to be attained. Substantial evidence indicates that the reinforcing properties of drugs of abuse, including nicotine, can be affected by the nitric oxide (NO) system, which may act by modulating central dopaminergic function. In this study, using single cell recordings in vivo coupled with microiontophoresis and microdialysis in freely moving animals, the role of NO signaling on the hyperacti…

A Diet for Dopaminergic Neurons?

Parkinson's disease (PD) is the second most common neurodegenerative disease, which unfortunately is still fatal. Since the discovery of dopamine (DA) neuronal cell loss within the substantia nigra in PD, the past decades have seen the understanding of the pathophysiological mechanisms underlying the degenerative process advance at a very impressive rate. Nevertheless, there is at present no cure for PD. Although there are no proven therapies for prevention, a large body of evidence from animal studies has highlighted the paramount role of dietary factors in counteracting DA degeneration. Consistently, associations between the risk of developing PD and the intake of nutrients, individual fo…

Behavioral fragmentation in the D1CT-7 mouse model of Tourette's syndrome.

Aim The transgenic D1CT-7 mouse is one of the best-characterized animal models of Tourette's syndrome (TS), exhibiting spontaneous tic-like Head-Body Twitches (HBT) and deficits in sensorimotor gating. This study is aimed at evaluating the behavioral dynamics of these mutants and their potential relevance to TS. Methods The behavior of D1CT-7 and Wild Type littermates was firstly assessed by considering frequencies and durations. To detect recurrent real-time behavioral sequences, the multivariate T-pattern analysis was employed. Analyses of transition probabilities among behaviors further provided an overall picture of the behavioral dynamics. Results T-patterns and transition matrices rev…

Non-steroidal anti-inflammatory drugs in Parkinson’s disease

Parkinson's disease (PD) is known to be a chronic and progressive neurodegenerative disease caused by a selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). A large body of experimental evidence indicates that the factors involved in the pathogenesis of this disease are several, occurring inside and outside the DAergic neuron. Recently, the role of the neuron–glia interaction and the inflammatory process, in particular, has been the object of intense study by the research community. It seems to represent a new therapeutic approach opportunity for this neurological disorder. Indeed, it has been demonstrated that the cyclooxygenase type 2 (COX-…

A Diet for Dopaminergic Neurons?

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which unfortunately is still fatal. Since the discovery of dopamine (DA) neuronal cell loss within the substantia nigra in PD, the past decades have seen the understanding of the pathophysiological mechanisms underlying the degenerative process advance at a very impressive rate. Nevertheless, there is at present no cure for PD. Although there are no proven therapies for prevention, a large body of evidence from animal studies has highlighted the paramount role of dietary factors in counteracting DA degeneration. Consistently, associations between the risk of developing PD and the intake of nutrients, individual fo…

ANTIOXIDANTS DIETERY INTAKE AND PARKINSON'S DISEASE

Cannabinoid 1/2 Receptor Activation Induces Strain-Dependent Behavioral and Neurochemical Changes in Genetic Absence Epilepsy Rats From Strasbourg and Non-epileptic Control Rats

Childhood absence epilepsy (CAE) is characterized by absence seizures, which are episodes of lack of consciousness accompanied by electrographic spike-wave discharges. About 60% of children and adolescents with absence seizures are affected by major neuropsychological comorbidities, including anxiety. Endocannabinoids and monoamines are likely involved in the pathophysiology of these CAE psychiatric comorbidities. Here, we show that the synthetic cannabinoid receptor type 1/2 (CB1/2R) agonist WIN 55,212-2 (2 mg/kg) has a strain-dependent effect on anxiety-like and motor behavior when assess in the hole board test and cerebral monoaminergic levels in Genetic Absence Epilepsy Rats from Strasb…

Will it ever become possible to prevent dopaminergic neuronal degeneration?

Parkinsons disease (PD) is the second leading age-related degenerative brain disease in the world affecting millions of people. This neurological disorder disrupts the quality of life of patients and their families, exerts an enormous emotional and physical strain on caregivers, and has a large cost for society. Moreover, the increasing numbers of elderly people in the population will result in a sharp increase in the prevalence of PD. The understanding of its pathophysiology and treatment has advanced at a very impressive rate during past decades. Nevertheless, PD is still fatal and there is at present no cure for it. Furthermore, there are no proven therapies for prevention of PD and alth…

Discovering hidden temporal patterns in behavior and interaction : t-pattern detection and analysis with THEME

In our laboratories we use T-pattern analysis to study rat behavior in different and well-known experimental assays widely employed as rodent models of anxiety: the open field, the hole board and the elevated plus maze. By using Theme software and T-pattern analysis, we have observed that numerous events, characterizing rodent behavior in each experimental model, occurred sequentially and with significant constraints on the interval lengths separating them. In this chapter, for each test, we highlight some key aspects of our behavioral analyses, with a twofold attempt: first to provide the researcher with useful information concerning the application of T-pattern analysis in the study of ro…

Acute inactivation of the medial forebrain bundle imposes oscillations in the SNr: a challenge for the 6-OHDA model?

It has been recently shown that the substantia nigra pars reticulata (SNr) of 6-hydroxydopamine (6-OHDA)-lesioned rats, under urethane anaesthesia, manifests a prominent low frequency oscillation (LFO) of around 1Hz, synchronized with cortical slow wave activity (SWA). Nevertheless, it is poorly understood whether these electrophysiological alterations are correlated only with severe dopamine depletion or may also play a relevant pathogenetic role in the early stages of the dopamine denervation. Hence, here we recorded SNr single units and electrocorticogram (ECoG) in two models of dopamine denervation: (i) acute dopamine denervated rats, obtained by injection of tetrodotoxin (TTX), (ii) ch…

Non-alcoholic fatty liver disease is associated with higher metabolic expenditure in overweight and obese subjects: A case-control study

Non-alcoholic fatty liver disease (NAFLD) is a common condition in Western countries. However, their metabolic characteristics are poorly known even though they could be important. Therefore, the objective of this study was to measure resting metabolic parameters in overweight/obese adults with hepatic steatosis compared to controls, matched for age, sex, and obesity level. Hepatic steatosis was diagnosed with liver ultrasound. Energy metabolism was measured with indirect calorimetry: energy expenditure (REE), predicted REE, the ratio between REE and the predicted REE, and the respiratory quotient (RQ) were reported. We measured some anthropometric, body composition, and bio-humoral paramet…

A. Chattopadhyah, Editor, Serotonin Receptors in Neurobiology, CRC Press, Taylor & Francis Group (2007) Price: £79.99, ISBN: 9780849339776.

Serotonin Receptors in Neurobiology, CRC Press, Taylor & Francis Group (2007)