Involvement of the opioid system in the anxiolytic-like effects induced by Δ9-tetrahydrocannabinol

Rationale: Recent studies have shown that several pharmacological actions induced by cannabinoids, including antinociception and reward, involve the participation of the endogenous opioid system. Objectives: The present study was designed to examine the possible involvement of the different opioid receptors in the anxiolytic-like responses induced by Delta(9)-tetrahydrocannabinol (THC). Methods: The administration of a low dose of THC (0.3 mg/kg) produced clear anxiolytic-like responses in the light-dark box, as previously reported. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, SR 141716A (0.5 mg/kg), or the mu-opioid receptor antagonist, beta-funaltrexamine (5 mg/kg), the delta-opioid receptor antagonist, naltrindole (2.5 mg/kg) and the kappa-opioid receptor antagonist, nor-binaltorphimine (2.5 mg/kg) were evaluated on anxiolytic-like responses induced by THC. Results: SR 141716A completely blocked the anxiolytic-like response induced by THC, suggesting that this effect is mediated by CB1 cannabinoid receptors. The p-opioid receptor antagonist beta-funaltrexamine and the delta-opioid receptor antagonist naltrindole, but not the kappa-opioid receptor antagonist norbinaltorphimine, abolished THC anxiolytic-like effects, suggesting an involvement of mu- and delta-opioid receptors in this behavioural response. Conclusions: These results demonstrate that the endogenous opioid system is involved in the regulation of anxiety-like behaviour by cannabinoids and provide new findings to clarify further the interaction between these two neuronal systems.