Varenicline and mecamylamine attenuate locomotor sensitization and cross-sensitization induced by nicotine and morphine in mice

The present study focused on the evaluation of behavioural sensitization and cross-sensitization induced by nicotine and morphine in mice. First, we revealed that after 9 days of nicotine administration (0.175 mg/kg, free base), every other day and following its 7-day withdrawal, challenge doses of nicotine (0.175 mg/kg) and morphine (5 mg/kg) induced locomotor sensitization in mice. When we examined the influence of varenicline, a partial alpha4beta2 nicotinic receptor agonist (0.5, 1 and 2 mg/kg) and mecamylamine (0.5, 1 and 2 mg/kg), a non-selective nicotinic receptor antagonist, we found that both agents attenuated the acquisition and expression of nicotine sensitization as well as locomotor cross-sensitization between nicotine and morphine. Our results indicate similar cholinergic mechanisms involved in the locomotor stimulant effects of nicotine and morphine in mice, and as such these data may suggest that nicotinic neurotransmission could be a potential target for developing pharmacotherapeutic strategies to treat and prevent nicotine and/or opioid addiction.