WorldCat Identities

Spampinato, Umberto

Overview
Works: 15 works in 19 publications in 2 languages and 22 library holdings
Roles: Thesis advisor, Opponent, Other
Publication Timeline
.
Most widely held works by Umberto Spampinato
Implication conditionnelle des récepteurs sérotoninergiques dans le contrôle de l'activité des voies dopaminergiques nigro-striée et méso-accumbale chez le rat by Grégory Porras( Book )

2 editions published in 2002 in French and held by 2 WorldCat member libraries worldwide

Etude in vivo du contrôle inhibiteur tonique et phasique exercé par les récepteurs sérotoninergiques de type 5-HT2c sur l'activité des voies dopaminergiques nigrostriée et mésoaccumbale chez le rat by Sylvia Navailles( Book )

2 editions published in 2005 in French and held by 2 WorldCat member libraries worldwide

This study, concerning the serotonergic 2C (5-HT2c) receptor, was aimed to go deeper into the mechanisms of the tonic and phasic inhibitory control exerted by this receptor on DA release measured by intracerebral microdialysis in the halothane-anesthetized rat nucleus accumbens (NAc) and striatum. By using appropriate pharmacological tools (agonist, inverse agonist, antagonist of 5-HT2c receptors), we explored 1) the participation of the constitutive activity of 5-HT2c receptors in vivo 2) the relevance of the degree of activity of mesolimbic and nigrostriatal DA neurons, and 3) the existence of region-dependant controls of the mesolimbic DA pathway. In both brain regions, the excitatory effect of the 5-HT2c inverse agonist SB 206553 on DA release is blocked by the 5-HT2c antahonist SB 242084 but not modified by the reduction of the central 5-HT tone. SB 206553, without effect on clozapine-stimulated DA release, potentiates haloperidol-induced DA release, whereas SB 242084, without effect on haloperidol, dose-dependently blocks the DA effect of clozapine. Both 5-HT2c ligands potentiate cocaine-stimulated DA release while the 5-HT2c agonist Ro 60-0175 does not affect the DA effect of cocaine but reduces that of haloperidol. Finally, the local application of 5-HT2c antagonists in the ventral tegmental area (VTA) and the NAc blocks the inhibition of accumbal DA release induced by the systemic administration of Ro 60-0175. These findings show that 1) the constititive activity of 5-HT2c receptors participates in the tonic inhibitory control of mesoaccumbal and nigrostriatal DA neurons in vivo ; 2) 5-HT2c receptors modulate DA exocytosis in a manner that is dependent of the degree of activation of ascending DA neurons ; 3) the 5-HT2c-dependent inhibitory control of the mesolimbic DA pathway is mediated, at least in part, by 5-HT2c receptors located in the VTA and the NAc. This work brings up new physiological and therapeutical perspectivesconcerning the role of 5-HT2c receptors in the basal ganglia
Etude des mécanismes de régulation des récepteurs 5-HT2C dans des modèles murins de troubles émotionnels by Cédric Bernard Pierre Martin( )

1 edition published in 2012 in French and held by 2 WorldCat member libraries worldwide

Pas de résumé en anglais
Serotonin2C receptors and drug addiction: focus on cocaine by Céline Devroye( )

1 edition published in 2013 in English and held by 2 WorldCat member libraries worldwide

Differential control of dopamine ascending pathways by serotonin2B receptor antagonists: New opportunities for the treatment of schizophrenia( )

1 edition published in 2016 in English and held by 1 WorldCat member library worldwide

Abstract: Recent studies suggest that the central serotonin2B receptor (5-HT2B R) could be an interesting pharmacological target for treating neuropsychiatric disorders related to dopamine (DA) dysfunction, such as schizophrenia. Thus, the present study was aimed at characterizing the role of 5-HT2B Rs in the control of ascending DA pathway activity. Using neurochemical, electrophysiological and behavioral approaches, we assessed the effects of two selective 5-HT2B R antagonists, RS 127445 and LY 266097, on invivo DA outflow in DA-innervated regions, on mesencephalic DA neuronal firing, as well as in behavioral tests predictive of antipsychotic efficacy and tolerability, such as phencyclidine (PCP)-induced deficit in novel object recognition (NOR) test, PCP-induced hyperlocomotion and catalepsy. Both RS 127445 (0.16mg/kg, i.p.) and LY 266097 (0.63mg/kg, i.p.) increased DA outflow in the medial prefrontal cortex (mPFC). RS 127445, devoid of effect in the striatum, decreased DA outflow in the nucleus accumbens, and potentiated haloperidol (0.1mg/kg, s.c.)-induced increase in mPFC DA outflow. Also, RS 127445 decreased the firing rate of DA neurons in the ventral tegmental area, but had no effect in the substantia nigra pars compacta. Finally, both RS 127445 and LY 266097 reversed PCP-induced deficit in NOR test, and reduced PCP-induced hyperlocomotion, without inducing catalepsy. These results demonstrate that 5-HT2B Rs exert a differential control on DA pathway activity, and suggest that 5-HT2B R antagonists could represent a new class of drugs for improved treatment of schizophrenia, with an ideal profile of effects expected to alleviate cognitive and positive symptoms, without eliciting extrapyramidal symptoms. Highlights: 5-HT2B R blockade increases and decreases DA outflow in the mPFC and NAc respectively. 5-HT2B R antagonists have no effect on striatal DA outflow and in the catalepsy test. 5-HT2B R antagonists reduce PCP-induced hyperlocomotion. 5-HT2B R antagonists reverse PCP-induced deficit in NOR. 5-HT2B R antagonists could be a new pharmacological tool for treating schizophrenia
Dynamics of hippocampal networks revealed by voltage sensitive dye imaging by Michelangelo Colavita( )

1 edition published in 2015 in English and held by 1 WorldCat member library worldwide

In order to better understand brain functioning we need to investigate all the structural domains present in it, from single cell to interconnected entire brain regions. However, while our knowledge in terms of single/few cells functioning is vast, very little is known about neuronal networks, which are interacting collections of neurons functionally related to the same task. Moreover, the balanced and concerted activity of excitatory and inhibitory networks plays a key role for proper cortical computations. However, while exist several tools to record excitatory networks activity, this is not the case for inhibitory networks. Voltage sensitive dye imaging (VSDI) is a technique that allows the recording of neuronal activity by mean of proportional emission of fluorescence according to changes in membrane potential. The advantage of using VSDI over other recording techniques using electrodes is that VSDI allows not invasive recording of neuronal activity from hundreds of sites at the same time. During my doctoral course I aimed at studying in detail excitatory and inhibitory neuronal networks in the CA1 area of mouse hippocampus with VSDI. To study excitatory networks more comprehensively, in collaboration with a team of mathematicians, we developed a mathematical algorithm that allowed measuring the velocity and the direction of spreading of the VSDI signal and it represents a new method to determine an optical flow. After successful validation of the algorithm with surrogate data to test its accuracy, we analysed two set of experiments in which network excitatory activity has been manipulated either by increasing Schaffer's collaterals stimulation intensity or by blocking GABAergic transmission with the GABAA receptor antagonist picrotoxin in order to increase the depolarization in the CA1 region of the hippocampus. The results of these manipulations significantly decreased signal velocity whereas picrotoxin application significantly modified the direction of spreading, making the depolarization-mediated VSDI signal less dispersed compared to control. Using VSDI I was able to fully characterize GABAA receptor-mediated hyperpolarizing signals in all the CA1 sublayers (field IPSPs), thus providing a new way of monitoring inhibitory events at network level. Moreover, I found that the activation of mGluR5 receptors induced an increase in a long-lasting manner of the VSDI-recorded field IPSPs, with duration and magnitude that relied on the specific CA1 sublayer considered. Overall, my work shows new methodologies and new findings that may represent a step forward in the quest for a better understanding of neuronal networks, both excitatory as well as inhibitory, which hopefully can contribute to reduce the gap of knowledge between single cell activity and behaviour
Central serotonin2B receptor blockade inhibits cocaine-induced hyperlocomotion independently of changes of subcortical dopamine outflow( )

1 edition published in 2015 in English and held by 1 WorldCat member library worldwide

Abstract: The central serotonin2B receptor (5-HT2B R) is currently considered as an interesting pharmacological target for improved treatment of drug addiction. In the present study, we assessed the effect of two selective 5-HT2B R antagonists, RS 127445 and LY 266097, on cocaine-induced hyperlocomotion and dopamine (DA) outflow in the nucleus accumbens (NAc) and the dorsal striatum of freely moving rats. The peripheral administration of RS 127445 (0.16mg/kg, i.p.) or LY 266097 (0.63mg/kg, i.p.) significantly reduced basal DA outflow in the NAc shell, but had no effect on cocaine (10mg/kg, i.p.)-induced DA outflow in this brain region. Also, RS 127445 failed to modify both basal and cocaine-induced DA outflow in the NAc core and the dorsal striatum. Conversely, both 5-HT2B R antagonists reduced cocaine-induced hyperlocomotion. Furthermore, RS 127445 as well as the DA-R antagonist haloperidol (0.1mg/kg, i.p.) reduced significantly the late-onset hyperlocomotion induced by the DA-R agonist quinpirole (0.5mg/kg, s.c.). Altogether, these results demonstrate that 5-HT2B R blockade inhibits cocaine-induced hyperlocomotion independently of changes of subcortical DA outflow. This interaction takes place downstream to DA neurons and could involve an action at the level of dorsostriatal and/or NAc DA transmission, in keeping with the importance of these brain regions in the behavioural responses of cocaine. Overall, this study affords additional knowledge into the regulatory control exerted by the 5-HT2B R on ascending DA pathways, and provides additional support to the proposed role of 5-HT2B Rs as a new pharmacological target in drug addiction. Highlights: Cocaine-induced striatal and accumbal DA outflow is unaltered by 5-HT2B R blockade. Cocaine-induced hyperlocomotion is inhibited by 5-HT2B R blockade. Quinpirole-induced late-onset hyperlocomotion is inhibited by 5-HT2B R blockade. 5-HT2B Rs could control cocaine-hyperlocomotion by acting downstream to DA neurons
Rôle des récepteurs sérotoninergique2B centraux dans la régulation des voies dopaminergiques ascendantes : implication dans les effets de la cocaïne by Adeline Cathala( )

1 edition published in 2021 in French and held by 1 WorldCat member library worldwide

My study on the functional role of the central serotoninergic receptor2B (5-HT2BR) is a logical continuation of the work already carried out in the laboratory. Recent results obtained in the laboratory have shown that 5-HT2BRs differentially modulate ascending dopaminergic (DA) pathways. Indeed, 5-HT2BR antagonist reduces DA release in the nucleus accumbens (NAc), increases DA release in the medial prefrontal cortex (mPFC), and had no effect on striatal DA release. This differential control on the DA system involves an interaction between 5-HT2BR in the dorsal raphe nucleus (DRN) and 5-HT1AR expressed in the mPFC, and results from an activation of DRN 5-HT neurons projecting to the mPFC. These results point out the DRN as the major site of action of 5-HT2BRs to the control of 5-HT and DA activity. In addition, it has been shown that 5-HT2BRs blockade control the neurochemical and behavioral responses induced by psychostimulants as amphetamine, 3,4-methylenedioxymethamphetamine and cocaine, one of the most worldwide abused drugs. Indeed, 5-HT2BR blockade suppresses cocaine-induced hyperlocomotion. This effect, which occurs independently of DA release in the NAc and striatum, where DA activity is tightly related to cocaine-induced behavioral reponses, likely involves post-synaptic interaction in subcortical DA brain regions. Nevertheless, (1) the involvement of mPFC DA release in this interaction remained to be determined, as this brain region is known for its anatomical and functional relationships with the NAc and striatum, and its involvement in cocaine-induced behavioral responses. (2) In addition, the cellular localization of 5-HT2BR within the DRN and the cellular mechanisms underlying their interactions between DA and 5-HT networks are unknown at the beginning of this study. Thus, the objective of this thesis is to answer the two points mentioned above. To this purpose, we assessed the effects of two potent and selective 5-HT2BR antagonists (RS 127445 and LY 266097) on 5-HT and DA activity, by using neurochemical, cellular and behavioral approaches in rats.In a first group of experiments, we provided anatomo-functional evidences showing that 5-HT2BR exert a GABA-mediated tonic inhibitory control on DRN 5-HT neurons innervating mPFC. This 5-HT control is a first step of a complex poly-synaptic regulation leading to differential control of DA mesocorticolimbic pathways. A second group of experiments shown that 5-HT2BR blockade inhibits cocaine-induced hyperlocomotion by acting at the level of DA neurotransmission in NAc, this effect resulting from the potentiation of cocaine-induced mPFC DA release.To conclude, the work accomplished over the past three years provides substantial information with regards to the functional role of 5-HT2BRs in the regulation of the activity of ascending DA pathways. Moreover, while improving the understanding of the interaction between DA and 5-HT systems, the present findings altogether highlight the therapeutic potential of 5-HT2BR antagonists for the treatment of cocaine addiction
Role of the central serotonin subscript 2B receptor in the regulation of ascending dopaminergic pathways : relevance for the treatment of schizophrenia and drug addiction by Celine Devroye( )

1 edition published in 2016 in English and held by 1 WorldCat member library worldwide

Four years ago, at the beginning of my thesis in Neuropharmacology, the functional role of the central serotonin2B receptor (5-HT2BR) remained poorly investigated. Indeed, in light of the relatively recent discovery of its presence in the mammalian brain, as compared to other 5-HT receptors, only few studies had explored its impact within the central nervous system. Interestingly, it had been shown that 5-HT2BRs, while having no effect at the level of the nigrostriatal dopaminergic (DA) pathway, afford a tonic excitatory control on the activity of the mesoaccumbal DA tract. This differential influence on subcortical DA brain regions had led to the proposal that 5-HT2BR antagonists may be a useful tool for improved treatment of DA-related disorders requiring an independent modulation of the activity of ascending DA pathways, such ass chizophrenia. However, the effect of 5-HT2BR blockade at the level of themesocortical DA pathway, which plays a pivotal role in the the rapeutic benefit of atypical antipsychotic drugs (APDs), had never been studied. In addition,analysis of the literature revealed that 5-HT2BR blockade suppresses amphetamine and 3,4-methylenedioxymethamphetamine-induced neurochemical and behavioral responses, suggesting that this receptor may also be a relevant pharmacological target for treating drug addiction. Nevertheless,its possible implication in the effects induced by cocaine, one of the most worldwide abused drugs, remained unknown.Thus, the aim of the present thesis was to study the regulatory control exerted by the 5-HT2BR on both basal and cocaine-induced stimulation of DA activity,in order to evaluate its therapeutic relevance for improved treatment of schizophrenia and drug abuse and dependence. To this purpose, we assessed the effects of potent and selective 5-HT2BR antagonists (RS 127445 and LY266097) on DA activity, by using biochemical, electrophysiological and behavioral approaches in rats.In a first group of experiments, we found that 5-HT2BRs exert a tonic inhibitory control on DA outflow in the medial prefrontal cortex (mPFC). This finding, by showing that 5-HT2BRs afford differential controls over the three ascending DA pathways, indicates that 5-HT2BR antagonists display an ideal pattern of effects to restore normal DA function in schizophrenia. Accordingly, 5-HT2BRantagonists were efficient in several behavioral models aimed at predicting APD efficacy, and had no effect in a behavioral task reflecting APD propensity to induce motor side effects. In a second group of experiments performed to determine the mechanisms under lying the differential control exerted by 5-HT2BRs on DA activity, we demonstrated that 5-HT2BR antagonist-induced opposite effects on DA ouflow in the mPFC and the nucleus accumbens (NAc)involve a functional interplay with 5-HT1ARs expressed in the mPFC. Finally,we found that 5-HT2BR blockade suppresses cocaine-induced hyperlocomotion.This effect, which occurs independently from changes of DA outflow in theNAc and the striatum, where DA activity is tightly related to cocaine-induced behavioral responses, likely involves a post-synaptic interaction in subcorticalDA brain regions.To conclude, the work accomplished over the past four years provides substantial information with regards to the functional role of 5-HT2BRs in the regulation of the activity of ascending DA pathways. In addition, while improving the understanding of the interaction between DA and 5-HT systems,the present findings altogether highlight the therapeutic potential of 5-HT2BRantagonists for treating schizophrenia and cocaine addiction
Serotonin2C receptor stimulation inhibits cocaine-induced Fos expression and DARPP-32 phosphorylation in the rat striatum independently of dopamine outflow( )

1 edition published in 2015 in English and held by 1 WorldCat member library worldwide

Abstract: The serotonin2C receptor (5-HT2C R) is known to control dopamine (DA) neuron function by modulating DA neuronal firing and DA exocytosis at terminals. Recent studies assessing the influence of 5-HT2C Rs on cocaine-induced neurochemical and behavioral responses have shown that 5-HT2C Rs can also modulate mesoaccumbens DA pathway activity at post-synaptic level, by controlling DA transmission in the nucleus accumbens (NAc), independently of DA release itself. A similar mechanism has been proposed to occur at the level of the nigrostriatal DA system. Here, using invivo microdialysis in freely moving rats and molecular approaches, we assessed this hypothesis by studying the influence of the 5-HT2C R agonist Ro 60-0175 on cocaine-induced responses in the striatum. The intraperitoneal (i.p.) administration of 1mg/kg Ro 60-0175 had no effect on the increase in striatal DA outflow induced by cocaine (15mg/kg, i.p.). Conversely, Ro 60-0175 inhibited cocaine-induced Fos immunoreactivity and phosphorylation of the DA and c-AMP regulated phosphoprotein of Mr 32kDa (DARPP-32) at threonine 75 residue in the striatum. Finally, the suppressant effect of Ro 60-0175 on cocaine-induced DARPP-32 phosphorylation was reversed by the selective 5-HT2C R antagonist SB 242084 (0.5mg/kg, i.p.). In keeping with the key role of DARPP-32 in DA neurotransmission, our results demonstrate that 5-HT2C Rs are capable of modulating nigrostriatal DA pathway activity at post-synaptic level, by specifically controlling DA signaling in the striatum. Highlights: The 5-HT2C R is known to control dopamine neuron function. The 5-HT2C R may control the effects of cocaine at postsynaptic level in the striatum. Cocaine-induced striatal DA outflow is unaltered by Ro 60-0175. Cocaine-induced striatal DARPP-32 phosphorylation is inhibited by Ro 60-0175. Cocaine behavioral effects may involve the 5-HT2C R control of striatal DA signaling
Role of pregnenolone derivative AEF0117 on the regulation of CB1 signaling that mediates behavioral effects of THC by Giovanni Tomaselli( )

1 edition published in 2020 in English and held by 1 WorldCat member library worldwide

 
moreShow More Titles
fewerShow Fewer Titles
Audience Level
0
Audience Level
1
  General Special  
Audience level: 0.94 (from 0.88 for Serotonin2 ... to 0.97 for Serotonin2 ...)

Languages
French (11)

English (8)