THE SELECTIVE CANNABINOID ANTAGONIST SR 141716A BLOCKS CANNABINOID-INDUCED ANTINOCICEPTION IN RATS

The purported CB1 cannabinoid antagonist SR 141716A has proven to be a useful tool in the investigation of cannabinoid pharmacology. This an tagonist was employed in the present study to investigate the antinoci ceptive and cataleptic effects of cannabinoids after either systemic o r intracerebroventricular (ICV) administration. The antinociceptive po tency of systemically administered Delta(9)-tetrahydrocannabinol (Delt a(9)-THC) was decreased 18-fold by SR 141716A, from an ED50 value of 0 .3-5.1 ml/kg. Similarly, it completely blocked the antinociceptive eff ects of Delta(9)-THC and CP 55,940, a potent bicyclic cannabinoid, aft er ICV administration. In addition, it prevented cannabinoid-induced c atalepsy when given by either route of administration. In contrast, SR 141716A failed to antagonize the antinociceptive effects of morphine, indicating its selectivity for cannabinoid receptors. These findings indicate that the antinociceptive and cataleptic effects of Delta(9)-T HC and CP 55,940 are mediated through CB1 cannabinoid receptors. (C) 1 997 Elsevier Science Inc.