SEROTONIN(1B) RECEPTOR STIMULATION ENHANCES DOPAMINE-MEDIATED REINFORCEMENT

The effect of 5-HT1B receptor stimulation on dopamine-mediated reinfor cement in rats was investigated using intravenous self-administration of the selective dopamine uptake inhibitor GBR-12909 on an FR5 schedul e of reinforcement. Pretreatment with the 5-HT1A/1B receptor agonist C GS-12066B (1-10 mg/kg, IP) dose-dependently reduced the self-administr ation of GBR-12909 (83 mu g/injection) by increasing the interval betw een drug injections, consistent with a enhancement of the reinforcing effects of GBR-12909. Additionally, CGS-12066B pretreatment (3 mg/kg, IP) shifted the dose-effect function for GBR-12909 self-administration to the left. Pretreatment with the selective 5-HT1A receptor agonist 8-OH-DPAT (0.03-1.0 mg/kg, SC) had no significant effect on GBR-12909 self-administration (83 mu g/injection), indicating that the effect of CGS-12066B is not mediated by the 5-HT1A receptor. Finally, CGS-12066 B pretreatment (1-10 mg/kg, IP) did not alter the self-administration of cocaine (0.03-0.5 mg/injection), suggesting that the simultaneous s timulation of multiple 5-HT receptor subtypes by the indirect 5-HT ago nist properties of cocaine may mask the effect of 5-HT1B receptor stim ulation on DA-mediated reinforcement.