Involvement of opioid system in cognitive deficits induced by ∆⁹-tetrahydrocannabinol in rats.
Cannabis is a widely used illicit substance. ∆(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 mgkg) impairs spatial memory in the eight-arm radial maze, and that this memory disturbance was reversed by the cannabinoid CB(1) receptor antagonist rimonabant (0.1 mgkg), suggesting that the effect of THC is mediated through cannabinoid CB(1) receptors. The present study was designed to examine the possible involvement of opioid receptors in the THC-induced impairment of spatial memory. The effects of treatment with the nonselective opioid receptor antagonist naloxone (0.3 and 1 mgkg), the μ-opioid receptor antagonist β-funaltrexamine (0.3 and 1 mgkg), the δ-opioid receptor antagonist naltrindole (1 and 3 mgkg), and the κ-opioid receptor antagonist nor-binaltorphimine (0.03 and 0.1 mgkg) on the impairment of spatial memory induced by THC were evaluated using the eight-arm radial maze. The nonselective opioid receptor antagonist naloxone, the μ-opioid receptor antagonist β-funaltrexamine, and the κ-opioid receptor antagonist nor-binaltorphimine, but not the δ-opioid receptor antagonist naltrindole, attenuated THC-induced cognitive deficits, suggesting an involvement of μ- and κ-opioid receptors in this behavioral response. 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.