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

Neuropsychopharmacology. 2008 Jan;33(2):237-46. doi: 10.1038/sj.npp.1301414. Epub 2007 Apr 11.


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 microg/0.2 microl, but not 1 microg/0.2 microl, 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 microg/0.2 microl) did not modify the effects of cocaine. Intra-NAc application of Ro 60-0175 dose-dependently excited (0.1 microM) and inhibited (1 microM) 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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Dopamine / metabolism*
  • Ethylamines / administration & dosage
  • Ethylamines / pharmacology
  • Indoles / administration & dosage
  • Indoles / pharmacology
  • Male
  • Microdialysis
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2C / drug effects
  • Receptor, Serotonin, 5-HT2C / physiology*
  • Serotonin Antagonists / pharmacology
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology*


  • 6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline
  • Aminopyridines
  • Ethylamines
  • Indoles
  • Receptor, Serotonin, 5-HT2C
  • Ro 60-0175
  • Serotonin Antagonists
  • Cocaine
  • Dopamine