Biochemical and electrophysiological evidence that RO 60-0175 inhibits mesolimbic dopaminergic function through serotonin(2C) receptors

• Published in: Brain research 2000-05, Vol.865 (1), p.85-90
• Main Authors: Di Matteo, V, Di Giovanni, G, Di Mascio, M, Esposito, E
• Format: Article
• Language: English
• Subjects: Animals; Dopamine - metabolism; Dose-Response Relationship, Drug; Electrophysiology; Ethylamines - pharmacology; Indoles - pharmacology; Limbic System - cytology; Limbic System - drug effects; Limbic System - metabolism; Male; Microdialysis; Neurons - drug effects; Neurons - metabolism; Nucleus Accumbens - cytology; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2B; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; Serotonin Receptor Agonists - pharmacology; Ventral Tegmental Area - cytology; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - metabolism
• ISSN: 0006-8993
• DOI: 10.1016/S0006-8993(00)02246-0

In vivo microdialysis and electrophysiological techniques were used to elucidate the role of the 5-HT(2) receptor family on the control of mesolimbic dopaminergic system exerted by serotonin (5-HT). Administration of RO 60-0175 (1 mg/kg, i.p.), a selective 5-HT(2C) receptor agonist, significantly decreased dopamine (DA) release by 26+/-4% (below baseline) 60 min after injection. Moreover, RO 60-0175 (80-320 microg/kg, i.v.) dose-dependently decreased the basal firing rate of DA neurons in the ventral tegmental area (VTA), reaching its maximal inhibitory effect (53.9+/-15%, below baseline) after the dose of 320 microg/kg. The selective 5-HT(2C) receptor antagonist SB 242084 completely blocked the inhibitory action of RO 60-0175 on accumbal DA release and on the firing rate of VTA DA cells. On the contrary, both (+/-)-DOI, a mixed 5-HT(2A/2C) receptor agonist, and the selective 5-HT(2B) agonist BW 723C86, did not affect either DA release in the nucleus accumbens or the firing rate of VTA DA cells. Taken together, these data confirm that central 5-HT system exerts an inhibitory control on the mesolimbic DA system and that 5-HT(2C) receptors are involved in this effect.