Dopamine D 2 receptor antagonists prevent Δ 9-tetrahydrocannabinol-induced antinociception in rats

Abstract

Δ 9-Tetrahydrocannabinol (1 and 5 mg/kg, i.p.) produced, dose-dependently, antinociceptive effects using hot plate and tail flick tests in rats. These effects were suppressed not only by the cannabinoid CB 1 receptor antagonist SR 141716A (0.5 mg/kg; i.p.) but also by the dopamine D 2 receptor antagonists S(−)-sulpiride (5 and 10 mg/kg; i.p.) and S(−)-raclopride (1.5 and 3 mg/kg; i.p.). Conversely, Δ 9-tetrahydrocannabinol antinociceptive effects were potentiated by the dopamine D 2 receptor agonists (−)-quinpirole (0.025 mg/kg, s.c.) and (+)-bromocriptine (0.5 and 1 mg/kg; i.p.). Our results indicate that the antinociceptive effects of Δ 9-tetrahydrocannabinol are mediated by the concomitant activation of cannabinoid CB 1 and dopamine D 2 receptors and that dopamine D 2 receptor agonists may be useful in improving the analgesic effects of cannabinoids.