Serotonin2C receptors in the medial prefrontal cortex facilitate cocaine-induced dopamine release in the rat nucleus accumbens.
A functional balance between excitatory and inhibitory control over dopamine (DA)-dependent behavioral and neurochemical effects of cocaine is afforded by the serotonin(2C) receptor (5-HT(2C)R) located within the ventral tegmental area and the nucleus accumbens (NAc). The 5-HT(2C)R located in the medial prefrontal cortex (mPFC) has also been shown to inhibit cocaine-induced behaviors perhaps through inhibition of DA function in the NAc. Using in vivo microdialysis in halothane-anesthetized rats, we tested this hypothesis by assessing the influence of mPFC 5-HT(2C)Rs on cocaine-induced DA outflow in the NAc shell. Intra-mPFC injection of the 5-HT(2C)R agonist Ro 60-0175 at 5 microg/0.2 microl, but not 1 microg/0.2 microl, potentiated the increase in accumbal DA outflow induced by the intraperitoneal administration of 10 mg/kg of cocaine. Conversely, cocaine-induced accumbal DA outflow was significantly reduced by the intra-mPFC injection of the selective 5-HT(2C)R antagonist SB 242084 (0.5 microg/0.2 microl) or SB 243213 (0.5 and 1 microg/0.2 microl). These results show that mPFC 5-HT(2C)Rs exert a positive control over cocaine-induced accumbal DA outflow. Observations further support the idea that the overall action of central 5-HT(2C)Rs on accumbal DA output is dependent on the functional balance among different 5-HT(2C)R populations located within the mesocorticoaccumbens system, and that 5-HT(2C)Rs can modulate DA-dependent behaviors independently of changes of accumbal DA release itself.
Leggio
Gian Marco
GM
Inserm U862, Neurocentre Magendie, Physiopathology of Addiction Group, Bordeaux F-33000, France. umberto.spampinato@inserm.fr
Cathala
Adeline
A
Moison
Delphine
D
Cunningham
Kathryn A
KA
Piazza
Pier Vincenzo
PV
Spampinato
Umberto
U
D000631:Aminopyridines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004563:Electrochemistry / Q000379:methods; D005021:Ethylamines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D018765:Dopamine Uptake Inhibitors; D005021:Ethylamines; D007211:Indoles; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; C103848:Ro 60-0175; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D003042:Cocaine; C406343:SB 243213; D004298:Dopamine