Rationale: Cannabis is a widely used illicit substance. Δ 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 CB 1 receptor antagonist rimonabant (0.1 mg/kg), suggesting that the effect of THC is mediated through cannabinoid CB 1 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 μ-opioid receptor antagonist β-funaltrexamine (0.3 and 1 mg/kg), the δ-opioid receptor antagonist naltrindole (1 and 3 mg/kg), and the κ-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 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. 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.
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