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

Abstract

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 μg/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 μg/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.