Effects of systemic 5-HT1B receptor compounds on ventral tegmental area intracranial self-stimulation thresholds in rats

Serotonin 1B (5-HT1B) receptors may play a role in regulating motivation and reward-related behaviours. To date, no studies have investigated the effects of the highly selective 5-HT1B receptor agonist CP 94253, on the reward model of ventral tegmental area intracranial self-stimulation. The current study investigated the hypothesis that 5-HT1B receptors play an inhibitory role in ventral tegmental area ICSS. Using Sprague–Dawley rats, the effects of the selective 5-HT1B receptor agonist CP 94253 (0–5.0 mg/kg) and the 5-HT1B/1D receptor antagonist GR 127935 (10.0 mg/kg) were investigated in rats trained to respond for ventral tegmental area ICSS; results were compared using rate-frequency threshold analysis. The highest dose of CP 94253 (5.0 mg/kg) tested in ventral tegmental area ICSS produced an increase in rate-frequency thresholds without affecting maximal response rates. This effect was attenuated by GR 127935 which did not show any effects when administered alone. These results suggest that 5-HT1B receptors play an inhibitory role in regulating ventral tegmental area ICSS.