0000000000702076
AUTHOR
Massimo Pierucci
showing 35 related works from this author
Serotonin control of central dopaminergic function: focus on in vivo microdialysis studies
2008
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…
The neurobiological bases for the pharmacotherapy of nicotine addiction.
2007
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…
Nitric oxide modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders.
2011
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…
Impact of serotonin 2C receptor null mutation on physiology and behavior associated with nigrostriatal dopamine pathway function.
2009
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…
Lateral Habenula 5-HT2C Receptor Function Is Altered by Acute and Chronic Nicotine Exposures
2021
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
2006
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…
High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo.
2013
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
2009
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…
Involvement of Nitric Oxide in Nigrostriatal Dopaminergic System Degeneration : A Neurochemical Study.
2009
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…
Nicotine modulation of the lateral habenula/ventral tegmental area circuit dynamics: An electrophysiological study in rats
2022
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…
Serotonin–dopamine interaction: electrophysiological evidence
2008
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…
The unilateral nigral lesion induces dramatic bilateral modification on rat brain monoamine neurochemistry
2009
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 dopaminergic neurons against MPP+-induced degeneration: an in vivo microdialysis study.
2007
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
2020
Nicotine addiction is a serious public health problem causing millions of deaths worldwide. Serotonin (5-hydroxytryptamine
Role(s) of the 5-HT2C receptor in the development of maximal dentate activation in the hippocampus of anesthetized rats.
2014
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.
2019
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…
2015
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 …
Author Correction: The FAAH inhibitor URB597 suppresses hippocampal maximal dentate afterdischarges and restores seizure-induced impairment of short …
2018
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.
Intake of Tomato-Enriched Diet Protects from 6-Hydroxydopamine-Induced Degeneration of Rat Nigral Dopaminergic Neurons
2009
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 …
Selective activation of 5-HT(2C) receptors stimulates GABA-ergic function in the rat substantia nigra pars reticulata: a combined in vivo electrophys…
2007
In vivo electrophysiology and microdialysis were used to investigate the physiological role of 5-HT(2C) 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-HT(2C) receptor agonist (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C(4)H(4)O(4) (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 …
Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus: Implicatio…
2009
Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine acting on two distinct receptor subtypes, namely p55 and p75 receptors. TNF-alpha p55 and p75 receptor knockout mice were previously shown to display a decreased or enhanced susceptibility to seizures, respectively, suggesting intrinsic modifications in neuronal excitability. We investigated whether alterations in glutamate system function occur in these naive knockout mice with perturbed cytokine signaling that could explain their different propensity to develop seizures. Using Western blot analysis of hippocampal homogenates, we found that p55(-/-) mice have decreased levels of membrane GluR3 and NR1 glutamate receptor subuni…
Preferential Modulation of the GABAergic vs. Dopaminergic Function in the Substantia Nigra by 5-HT2C Receptor
2009
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…
The FAAH inhibitor URB597 suppresses hippocampal maximal dentate afterdischarges and restores seizure-induced impairment of short and long-term synap…
2017
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…
Critical role of Nitric Oxide on Nicotine-Induced Hyperactivation of Dopaminergic Nigrostriatal System: Electrophysiological and Neurochemical eviden…
2010
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…
Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders
2008
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…
Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats
2019
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?.
2006
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…
The impact of chronic daily nicotine exposure and its overnight withdrawal on the structure of anxiety-related behaviors in rats: Role of the lateral…
2021
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…
Hsp60 response in experimental and human temporal lobe epilepsy
2015
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 …
Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study.
2006
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 Dopami…
2009
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
2020
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…
Non-steroidal anti-inflammatory drugs in Parkinson’s disease
2007
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-…
Hsp60 response in experimental and human temporal lobe epilepsy due to hyppocampal sclerosis
2015
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…
Critical role of nitric oxide on nicotine-induced hyperactivation of dopaminergic nigrostriatal system: electrophysiological and neurochemical eviden…
2010
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…