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

Abstract

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 Δ⁹-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 µ-opioid receptor antagonist, β-funaltrexamine (5 mg/kg), the δ-opioid receptor antagonist, naltrindole (2.5 mg/kg) and the κ-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 µ-opioid receptor antagonist β-funaltrexamine and the δ-opioid receptor antagonist naltrindole, but not the κ-opioid receptor antagonist nor-binaltorphimine, abolished THC anxiolytic-like effects, suggesting an involvement of µ- and δ-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.