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

Sylvia Navailles, Delphine Moison, Kathryn Cunningham, Umberto Spampinato

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Stimulation of central serotonin2C receptor (5-HT2CR) inhibits dopamine (DA)-dependent neurochemical and behavioral effects of cocaine, while 5-HT2CRs 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-HT2CRs in the VTA and the NAc to inhibit and enhance respectively cocaine-induced accumbal DA outflow. Intra-VTA injection of the 5-HT 2CR agonist Ro 60-0175 at 5 μg/0.2 μl, but not 1 μg/0.2 μl, 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 2CR antagonist SB 242084 at either dose (0.1 or 0.5 μg/0.2 μl) did not modify the effects of cocaine. Intra-NAc application of Ro 60-0175 dose-dependently excited (0.1 μM) and inhibited (1 μM) 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 2CRs on accumbal DA output is dependent, at least in part, on the functional balance between different 5-HT2CR populations within the NAc and within the mesoaccumbens DA pathway (VTA vs NAc).

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalNeuropsychopharmacology
Volume33
Issue number2
DOIs
StatePublished - Jan 2008

Fingerprint

Tegmentum Mesencephali
Ventral Tegmental Area
Microdialysis
Nucleus Accumbens
Cocaine
Dopamine
Serotonin Receptor Agonists
Serotonin Antagonists
Injections
Halothane
Serotonin

Keywords

  • 5-HT receptor
  • Accumbal dopamine release
  • Cocaine
  • Nucleus accumbens
  • Rat
  • Ventral tegmental area

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "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",
abstract = "Stimulation of central serotonin2C receptor (5-HT2CR) inhibits dopamine (DA)-dependent neurochemical and behavioral effects of cocaine, while 5-HT2CRs 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-HT2CRs in the VTA and the NAc to inhibit and enhance respectively cocaine-induced accumbal DA outflow. Intra-VTA injection of the 5-HT 2CR agonist Ro 60-0175 at 5 μg/0.2 μl, but not 1 μg/0.2 μl, 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 2CR antagonist SB 242084 at either dose (0.1 or 0.5 μg/0.2 μl) did not modify the effects of cocaine. Intra-NAc application of Ro 60-0175 dose-dependently excited (0.1 μM) and inhibited (1 μM) 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 2CRs on accumbal DA output is dependent, at least in part, on the functional balance between different 5-HT2CR populations within the NAc and within the mesoaccumbens DA pathway (VTA vs NAc).",
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