5-HT2A and 5-HT2C/2B Receptor Subtypes Modulate Dopamine Release Induced in Vivo by Amphetamine and Morphine in Both the Rat Nucleus Accumbens and Striatum

Porras, Grégory; Matteo, Vincenzo Di; Fracasso, Claudia; Lucas, George L.; Deurwaerdère, Philippe De; Caccia, Silvio; Esposito, Ennio; Spampinato, Umberto

doi:10.1016/s0893-133x(01)00333-5

Cited by 199 publications

(182 citation statements)

References 51 publications

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“…In the present study, the use of anesthesia allowed us to inject simultaneously into the VTA specific 5-HT 2C R drugs and monitor their effects on cocaine-induced DA release in the NAc via a dialysis cannula. Nevertheless, previous studies reporting similar modulatory effects of the 5-HT system on striatal and accumbal DA release in either freely moving or anesthetized rats, strongly suggest that anesthesia does not alter the responsiveness of midbrain DA neurons to 5-HT system modulation (Porras et al, 2002). Thus, within the limits of the different experimental design used, our data suggest that the modulation of cocaine-induced accumbal DA efflux triggered by intra-VTA administration of a 5-HT 2C R agonist or antagonist (present results) could, at least in part, participate in the parallel changes observed in the behavioral responses (Fletcher et al, 2004;McMahon et al, 2001).…”

Section: Discussionmentioning

confidence: 82%

“…These effects are most likely due to the actions of these compounds at 5-HT 2C R, but not 5-HT 2A R or 5-HT 2B R. Indeed, Ro 60-0175 displays 30-fold higher affinity for the 5-HT 2C R over the 5-HT 2A R (Martin et al, 1998) and SB 242084 shows 160-fold higher affinity for the 5-HT 2C R over the 5-HT 2A R (Kennett et al, 1997). Moreover, at variance with the proposed inhibitory role for 5-HT 2C R, the 5-HT 2A R exerts facilitatory control over activated mesoaccumbens DA function (Auclair et al, 2004;Broderick et al, 2004;Porras et al, 2002). Finally, while both compounds also bind to the 5-HT 2B R, this subtype is not expressed into the NAc (Duxon et al, 1997) and has no influence on the neuronal activity of DA neurons (Di Matteo et al, 2000;Gobert et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Dialysate samples were immediately analyzed by reversephase high-performance liquid chromatography coupled with electrochemical detection, as described previously (Porras et al, 2002). The mobile phase (containing (in mM) 70 NaH 2 PO 4 , 0.1 Na 2 EDTA, 0.7 triethylamine, and 0.1 octylsulfonic acid plus 10% methanol, adjusted to pH 4.8 with orthophosphoric acid) was delivered at 1 ml/min flow rate (system LC-10AD-VP, Shimadzu, Champs s/Marne, France) through a Hypersyl column (C 18 ; 4.6 Â 150 mm, particle size 5 mm; Touzard & Matignon, Paris, France).…”

Section: Chromatographic Analysismentioning

confidence: 99%

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Differential Regulation of the Mesoaccumbens Dopamine Circuit by Serotonin2C Receptors in the Ventral Tegmental Area and the Nucleus Accumbens: An In Vivo Microdialysis Study with Cocaine

Navailles

Moison

Cunningham

et al. 2007

Neuropsychopharmacol

100

102

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Stimulation of central serotonin2C receptor (5-HT 2C R) inhibits dopamine (DA)-dependent neurochemical and behavioral effects of cocaine, while 5-HT 2C Rs locally expressed into the ventral tegmental area (VTA) and the nucleus accumbens (NAc) exert opposite functional control over cocaine-induced behavioral effects. Using in vivo microdialysis in halothane-anesthetized rats, we tested the hypothesis that this functionally opposite regulation of the mesoaccumbens DA pathway relies on the ability of 5-HT 2C Rs in the VTA and the NAc to inhibit and enhance respectively cocaine-induced accumbal DA outflow. Intra-VTA injection of the 5-HT 2C R agonist Ro 60-0175 at 5 mg/0.2 ml, but not 1 mg/0.2 ml, attenuated the increase in accumbal DA outflow induced by the systemic administration of 10 mg/ kg of cocaine. Intra-VTA injection of the 5-HT 2C R antagonist SB 242084 at either dose (0.1 or 0.5 mg/0.2 ml) did not modify the effects of cocaine. Intra-NAc application of Ro 60-0175 dose-dependently excited (0.1 mM) and inhibited (1 mM) cocaine-induced DA outflow. In contrast, intra-NAc application of SB 242084 resulted in diametrically opposite effects when applied at these concentrations. These results further support the idea that the overall action of central 5-HT 2C Rs on accumbal DA output is dependent, at least in part, on the functional balance between different 5-HT 2C R populations within the NAc and within the mesoaccumbens DA pathway (VTA vs NAc).

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Chromatographic Analysismentioning

confidence: 99%

See 1 more Smart Citation

Differential Regulation of the Mesoaccumbens Dopamine Circuit by Serotonin2C Receptors in the Ventral Tegmental Area and the Nucleus Accumbens: An In Vivo Microdialysis Study with Cocaine

Navailles

Moison

Cunningham

et al. 2007

Neuropsychopharmacol

100

102

View full text Add to dashboard Cite

show abstract

“…VTA DA projection neurons are under inhibitory control by 5-HT, mediated by 5-HT 2C receptors . 5-HT 2A and 5-HT 2C receptors modulate DA release induced by amphetamine and morphine, respectively, in the NAC and striatum, and 5-HT 2C receptors selectively modulate the impulse-flow-dependent release of DA (Porras et al, 2002). Volkow and Fowler (2000) provide evidence that the orbital PFC is hypoactive relative to the levels of DA D2 receptors in the ventral striatum in addicted individuals during protracted withdrawal.…”

Section: Da Dysfunction In Alcoholismmentioning

confidence: 87%

Dopamine Dysfunction in Borderline Personality Disorder: A Hypothesis

Friedel

2004

Neuropsychopharmacol

123

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Research on the biological basis of borderline personality disorder (BPD) has focused primarily on the serotonin model of impulsive aggression. However, there is evidence that dopamine (DA) dysfunction may also be associated with BPD. Pertinent research and review articles, identified by Medline searches of relevant topics, books, references from bibliographies, and conference proceedings from 1975 to 2003, were reviewed. Evidence of DA dysfunction in BPD derives from the efficacy of traditional and atypical antipsychotic agents in BPD, and from provocative challenges with amphetamine and methylphenidate of subjects with the disorder. In addition, human and animal studies indicate that DA activity plays an important role in emotion information processing, impulse control, and cognition. The results of this review suggest that DA dysfunction is associated with three dimensions of BPD, that is, emotional dysregulation, impulsivity, and cognitive-perceptual impairment. The main limitation of this hypothesis is that the evidence reviewed is circumstantial. There is no study that directly demonstrates DA dysfunction in BPD. In addition, the therapeutic effects of antipsychotic agents observed in BPD may be mediated by non-DA mechanisms of action. If the stated hypothesis is correct, DA dysfunction in BPD may result from genetic, developmental, or environmental factors directly affecting specific DA pathways. Alternatively, DA dysfunction in BPD may be a compensatory response to alterations in the primary neural systems that control emotion, impulse control, and cognition, and that are mediated by the brain's main neurotransmitters, glutamate, and GABA, or in one or more other neuromodulatory pathways such as serotonin, acetylcholine, and norepinephrine.

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“…115 Serotonin levels are increased by nicotine administration and decreased during withdrawal. 116,117 The serotonin transporter gene (5-HTT or SLC6A4) has been implicated in a number of psychiatric disorders such as depression and schizophrenia, both of which have high rates of co-morbidity with smoking.…”

Section: Serotonin Systemmentioning

confidence: 99%

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

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5-HT2A and 5-HT2C/2B Receptor Subtypes Modulate Dopamine Release Induced in Vivo by Amphetamine and Morphine in Both the Rat Nucleus Accumbens and Striatum

Abstract: In vivo microdialysis and single-cell extracellular recordings were used to assess the involvement of

Cited by 199 publications

References 51 publications

Differential Regulation of the Mesoaccumbens Dopamine Circuit by Serotonin2C Receptors in the Ventral Tegmental Area and the Nucleus Accumbens: An In Vivo Microdialysis Study with Cocaine

Differential Regulation of the Mesoaccumbens Dopamine Circuit by Serotonin2C Receptors in the Ventral Tegmental Area and the Nucleus Accumbens: An In Vivo Microdialysis Study with Cocaine

Dopamine Dysfunction in Borderline Personality Disorder: A Hypothesis

Overview of the pharmacogenomics of cigarette smoking

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