Involvement of opioid system in cognitive deficits induced by Δ9-tetrahydrocannabinol in rats

Rationale Cannabis is a widely used illicit substance. Delta(9)-Tetrahydrocannabinol (THC), the major psychoactive component of cannabis, is known to induce cognitive deficits that closely resemble the impairment observed in schizophrenic patients. We previously reported that THC (6 mg/kg) impairs spatial memory in the eight-arm radial maze, and that this memory disturbance was reversed by the cannabinoid CB1 receptor antagonist rimonabant (0.1 mg/kg), suggesting that the effect of THC is mediated through cannabinoid CB1 receptors. Objectives The present study was designed to examine the possible involvement of opioid receptors in the THC-induced impairment of spatial memory. Methods The effects of treatment with the nonselective opioid receptor antagonist naloxone (0.3 and 1 mg/kg), the mu-opioid receptor antagonist beta-funaltrexamine (0.3 and 1 mg/kg), the delta-opioid receptor antagonist naltrindole (1 and 3 mg/kg), and the kappa-opioid receptor antagonist nor-binaltorphimine (0.03 and 0.1 mg/kg) on the impairment of spatial memory induced by THC were evaluated using the eight-arm radial maze. Results The nonselective opioid receptor antagonist naloxone, the mu-opioid receptor antagonist beta-funaltrexamine, and the kappa-opioid receptor antagonist nor-binaltorphimine, but not the delta-opioid receptor antagonist naltrindole, attenuated THC-induced cognitive deficits, suggesting an involvement of mu- and kappa-opioid receptors in this behavioral response. Conclusions These results demonstrate that the endogenous opioid system is involved in the regulation of the acute short-term and working memory deficits induced by cannabis.