Effects of systemic and intra-nucleus accumbens 5-HT2C receptor compounds on ventral tegmental area self-stimulation thresholds in rats

Serotonin 2C (5-HT2C) receptors may play a role in regulating motivation and reward-related behaviours. To date, no studies have investigated the possible role of 5-HT2C receptors in ventral tegmental area (VTA) intracranial self-stimulation (ICSS). The current study investigated the hypotheses that 5-HT2C receptors play an inhibitory role in VTA ICSS, and that 5-HT2C receptors within the nucleus accumbens (NAc) shell may be involved. Male Sprague-Dawley rats were implanted with a VTA electrode and bilateral NAc shell cannulae for the experiment involving microinjections, and trained to respond for electrical self-stimulation. The systemic effects of the selective 5-HT2C receptor agonist WAY 161503 (0-1.0 mg/kg), the 5-HT1A/1B/2C receptor agonist TFMPP (0.3 mg/kg) and the selective 5-HT2C receptor antagonist SB 242084 (1.0 mg/kg) were compared using rate-frequency threshold analysis. Intra-NAc shell microinjections of WAY 161503 (0-1.5 mu g/side) were investigated and compared to amphetamine (1.0 mu g/side). WAY 161503 (1.0 mg/kg) and TFMPP (0.3 mg/kg) significantly increased rate-frequency thresholds (M50 values) without altering maximal response rates (RMAX values). SB 242084 attenuated the effects of TFMPP; SB 242084 had no affect on M50 or RMAX values. Intra-NAc shell WAY 161503 had no effect on M50 or RMAX values; intra-NAc amphetamine decreased M50 values. These results suggest that 5-HT2C receptors play an inhibitory role in regulating reward-related behaviour while 5-HT2C receptor activation in the NAc shell did not appear to influence VTA ICSS behaviour under the present experimental conditions.