Biochemical and electrophysiological evidence that RO 60-0175 inhibits mesolimbic dopaminergic function through serotonin2C receptors

In vivo microdialysis and electrophysiological techniques were used to elucidate the role of the 5-HT2 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-HT2C receptor agonist, significantly decreased dopamine (Dh) release by 26+/-4% (below baseline) 60 min after injection. Moreover, RO 60-0175 (80-320 mu g/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 mu g/kg. The selective 5-HT,, receptor antagonist SE 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-HT2A/2C receptor agonist, and the selective 5-HT2B 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-HT2C receptors are involved in this effect. (C) 2000 Elsevier Science B.V. All rights reserved.