Serotonin1B receptor stimulation enhances dopamine-mediated reinforcement

Abstract

The effect of 5-HT_1B receptor stimulation on dopamine-mediated reinforcement in rats was investigated using intravenous self-administration of the selective dopamine uptake inhibitor GBR-12909 on an FR5 schedule of reinforcement. Pretreatment with the 5-HT_1A/1B receptor agonist CGS-12066B (1–10 mg/kg, IP) dose-dependently reduced the self-administration of GBR-12909 (83 μg/injection) by increasing the interval between 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-HT_1A receptor agonist 8-OH-DPAT (0.03– 1.0 mg/kg, SC) had no significant effect on GBR-12909 self-administration (83 μg/injection), indicating that the effect of CGS-12066B is not mediated by the 5-HT_1A receptor. Finally, CGS-12066B pretreatment (1–10 mg/kg, IP) did not alter the self-administration of cocaine (0.03–0.5 mg/injection), suggesting that the simultaneous stimulation of multiple 5-HT receptor subtypes by the indirect 5-HT agonist properties of cocaine may mask the effect of 5-HT_1B receptor stimulation on DA-mediated reinforcement.