The effect of serotonergic agents on haloperidol-induced striatal dopaminerelease in vivo: opposite role of 5-HT2A and 5-HT2C receptor subtypes and significance of the haloperidol dose used

This study investigated, using microdialysis in freely-moving rats, the rol e of serotonin (5-HT) and 5-HT2 receptor subtypes in the enhancement of str iatal dopamine (DA) release induced by various doses of haloperidol. The subcutaneous injection of 0.01, 0.1 or 1 mg/kg haloperidol dose-depende ntly increased DA outflow (160, 219 and 230% of baseline, respectively). Th e effect of 0.01 mg/kg haloperidol was, respectively, potentiated by the 5- HT uptake inhibitor citalopram (1 mg/kg, s.c.; +35%) and reduced by the 5-H T1A receptor agonist 8-OH-DPAT (0.025 mg/kg, s.c.; -32%). Also, it was redu ced by the 5-HT2A antagonist SR 46349B (0.5 mg/kg, s.c.; -40%) or by the 5- HT2A/2B/2C antagonist ritanserin (1.25 mg/kg, i.p.; -34%), and potentiated by the 5-HT2B/2C antagonist SE 206553 (5 mg/kg, i.p; +78%). Further, only t his latter compound significantly modified basal dopamine release by itself (+26%). Dopamine released by 0.1 mg/kg haloperidol was enhanced (+100%) by citalopram, decreased (-61%) by SR 4634B, but unaltered by SE 206553. Fina lly, none of the compounds used were able to modify the enhancement of dopa mine release induced by 1 mg/kg haloperidol. These results show that central 5-HT2A and 5-HT2C receptors exert an opposi te (respectively excitatory and inhibitory) influence on DA release. Moreov er, they suggest that the 5-HT2A-dependent modulation depends on the degree of central DA receptor blockade. (C) 2000 Elsevier Science Ltd. All rights reserved.