Central Serotonin2C Receptor: From Physiology to Pathology

Giovanni, Giuseppe Di; Matteo, Vincenzo Di; Pierucci, Massimo; Benigno, Arcangelo; Esposito, Ennio

doi:10.2174/156802606778522113

Cited by 74 publications

(50 citation statements)

References 188 publications

(291 reference statements)

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“…The fact that 5-HT 2A , but not 5-HT 2C , receptors are responsive to L-DOPA treatment predicts that pharmacological manipulations at 5-HT 2C , but not at 5-HT 2A , will result in similar effects in PD patients whether they are treated or not with DA replacement. These data therefore support the notion that 5-HT 2C receptor antagonists may be useful as an adjuvant treatment to DA agonists to treat motor complications of PD (Fox et al, 1998;Di Giovanni et al, 2006a;.…”

Section: -Ht Receptors' Expression In Pd Animal Models and In Patientssupporting

confidence: 79%

“…The efficacy of the atypical APDs in treating psychosis in PD patients is likely to be due to their ability in blocking 5-HT receptors. In fact, antagonists or inverse agonists of the 5-HT 2A and 5-HT 2C receptor are potential therapeutic agents for treatment-induced psychosis of PD (Weiner et al, 2003;Di Giovanni et al, 2006a).…”

Section: Role Of 5-ht In Psychiatric Complications In Pdmentioning

confidence: 99%

“…It is thus likely that 5-HT plays a role in regulating the appropriate selection of voluntary movements by the basal ganglia, and abnormalities in 5-HT transmission might contribute to the neural mechanisms underlying disorders of basal ganglia origin, such as Parkinson's disease (PD), Tourette's syndrome and obsessive compulsive disorder (Chapter 24; Ring and Serra-Mestre, 2002). Indeed, biochemical evidence suggests that 5-HT transmission is abnormal in the basal ganglia of patients with PD (Hornykiewicz, 1998) and, moreover, in the movement abnormalities generally associated with the use of L-3,4-dihydroxyphenylalanine [levodopa (L-DOPA)] and classical antipsychotic drugs' (APDs) motor side effects (Bezard et al, 2001;Blackburn, 2004;Di Giovanni et al, 2006a;Chapters 22 and 23 in this volume).…”

Section: Introductionmentioning

confidence: 99%

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

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

130

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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 distribution of different 5-HT receptor subtypes in the basal ganglia nuclei will be described. Furthermore, evidence demonstrating the serotonergic control of basal ganglia activity will be reviewed and the contribution of the different 5-HT receptor subtypes examined. The new avenues that the increasing knowledge of 5-HT in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. It is clear that these avenues will be fruitful, despite the disappointing results so far obtained by clinical studies with selective 5-HT ligands. Nevertheless, these studies have led to a great increase in the attention given to the neurotransmitters of the basal ganglia and their connections.

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Section: -Ht Receptors' Expression In Pd Animal Models and In Patientssupporting

confidence: 79%

Section: Role Of 5-ht In Psychiatric Complications In Pdmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

130

View full text Add to dashboard Cite

show abstract

“…On the basis of this evidence there have been a number of recent suggestions that the 5-HT 2C receptor might be a valid target for the development of medications for treating drug abuse (Bubar and Cunningham, 2006;Di Giovanni et al, 2006;Higgins and Fletcher, 2003;Ji et al, 2006). In the present experiments, we have explored further the potential utility of a 5-HT 2C receptor agonist for drug abuse.…”

Section: Introductionmentioning

confidence: 91%

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Fletcher

Rizos

Sinyard

et al. 2007

Neuropsychopharmacol

112

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Previously, we showed that the 5-HT 2C receptor agonist Ro60-0175 reduces cocaine self-administration, and the ability of cocaine to reinstate responding after extinction of drug-seeking behavior. The present experiments extended these findings further by determining whether the effects of Ro60-0175 on self-administration were sustained with repeated treatment, and whether Ro60-0175 altered reinstatement induced by the pharmacological stressor yohimbine, or by the context in which self-administration occurred. In Experiment 1, Ro60-0175 (1 mg/kg, s.c.) reduced cocaine (0.25 mg/infusion) self-administration maintained by a progressive ratio schedule. This reduction was sustained over eight daily injections. In Experiment 2, rats self-administered cocaine in daily 2 h sessions for 15 days on a FR1 schedule. Following extinction, yohimbine (1 mg/kg, i.p.) reinstated responding, and this effect was reduced dose dependently by Ro60-0175 (0.3-3 mg/kg, s.c.). In Experiment 3, rats were trained to respond for cocaine on a FR1 schedule in a distinct environmental context (A); responding was then extinguished in a different context (B). Reinstatement tests occurred in either context A or B.Responding was reinstated only when rats were tested in the original self-administration context (A). This reinstatement was reduced dose dependently by Ro60-0175. All effects of Ro60-0175 were blocked by the 5-HT 2C receptor antagonist SB242084. Thus, Ro60-0175, acting via 5-HT 2C receptors, reduces cocaine self-administration and cocaine-seeking triggered by a stressor and by drug-associated cues. The effects of Ro60-0175 do not exhibit tolerance within the 8-day test period. These results indicate that selective 5-HT 2C receptor agonists may be a useful pharmacological strategy for treatment of drug abuse.

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“…Conditional expression of 5-HT 1A in hippocampal and cortical regions is sufficient to normalize anxietylike behavior in mutant mice. 178 Interestingly, the conditional loss of forebrain 5-HT 1A function does not induce the anxiety-like phenotype when the deletion 174,175 Receptor tyrosine kinase signaling, typified by BDNF (brain-derived neurotrophic factor), is shown in yellow. BDNF or other ligand binds a homo-or heterodimer of the receptor (for example, TrkB) that, in turn, phosphorylates proteins downstream, such as GRB2 (growth factor receptor-bound protein).…”

Section: Autism Candidate Genes and Synaptic Functionmentioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

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Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism.

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Central Serotonin2C Receptor: From Physiology to Pathology

Cited by 74 publications

References 188 publications

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

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

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Advances in behavioral genetics: mouse models of autism

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