Involvement of the opioid system in the effects induced by nicotine on anxiety-like behaviour in mice

Rationale: Recent studies have revealed the participation of the endogenous opioid system in several behavioural responses induced by nicotine including antinociception, rewarding properties, and physical drug dependence. Objectives: The present study was designed to examine the possible involvement of the various opioid receptors in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice. Methods: The acute administration of low (0.05) or high (0.8 mg/kg) doses of nicotine subcutaneously produced opposite effects in the elevated plus maze, i.e. anxiolytic- and anxiogenic-like responses, respectively. Animals were only exposed once to nicotine. The effects of the pretreatment with the mu-opioid receptor antagonist, beta-funaltrexamine (5 mg/kg), the 5-opioid antagonist, naltrindole (2.5 mg/kg) and the kappa-opioid antagonist, nor-binaltorphimine (2.5 mg/kg) intraperitoneally were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine. Results: beta-funaltrexamine, but not nor-binaltorphimine or naltrindole, abolished nicotine-induced anxiolytic-like effects, suggesting an involvement of mu-opioid receptors in this behavioural. response. On the other hand, naltrindole, but not nor-binaltorphimine or beta-funaltrexamine, increased the anxiogenic-like responses of nicotine, suggesting an involvement of delta-receptors in this behavioural effect. Conclusions: These results demonstrate that the endogenous opioid system is involved in the effects induced by nicotine on anxiety-like behaviour and provide new findings to further clarify the interaction between these two neurochemical systems.