Anxiety does not affect the antinociceptive effect of Delta 9-THC in mice: participation of cannabinoid and opioid receptors.

Cannabinoid receptor agonists significantly inhibit nociceptive responses in a large number of animal models. The present study examined whether mice displaying different basal levels of anxiety in the plus-maze test of anxiety might differ in terms of responsiveness to the antinociceptive effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Further, the involvement of the cannabinoid and/or opioid receptors in Delta(9)-THC-induced antinociception was investigated by using SR 141716A and naloxone, respectively, cannabinoid and opioid receptor antagonists. Delta(9)-THC-induced antinociception was evaluated in the formalin test that involves a biphasic response with an early and a late phase of high paw-licking activity. This characteristic biphasic response was observed in all control animals selected as "anxious" and "nonanxious." Delta(9)-THC (0.5-5 mg/kg i.p.) caused a dose-dependent antinociceptive effect in both groups of mice during the early and late phases. This response was fully reversed by SR 141716A (1 mg/kg i.p.) and partially reversed by naloxone (2 mg/kg i.p.). These findings suggest that mice selected for differences in anxiety-related behavior show similar responses to the antinociceptive action of Delta(9)-THC and that this action involves predominantly cannabinoid mechanisms.