The mesolimbic dopamine system, the main neural system mediating sensitization, seems to overlap this mediating reward. Given some data indicating that dopamine neurons are effected by cholinergic neurotransmitters, the aim of present study was to determine the influence of varenicline, a partial α4β2 nicotinic receptor agonist (0.5, 1 and 2 mg/kg) and mecamylamine, a nonselective nicotinic receptor antagonist (0.5, 1 and 2 mg/kg) on behavioural sensitization and cross – sensitization induced by nicotine (0.175 mg/kg, base) and morphine (5 mg/kg) in mice. First, we revealed that repeated injections of nicotine (9 days, every other day) produced significant increase in locomotor activity in mice measured following 7-day withdrowal after injection of challange doses of nicotine and morphine. Subsequently, we found that varenicline and mecamylamine attenuated the acquisition and expression of nicotine sensitization as well as locomotor crosssensitization between nicotine and morphine. Because they had no effects on naive mice, we concluded that the ability of both agents to block this results did not correspond to general supression of activity. The development of nicotine locomotor sensitization shows similarity to relapse described in ex-smokers and cross – sensitization seems to reflect the phenomenon of simultaneous abuse of several different drugs. Our results indicate similar nicotinic neurotransmission - probably through the α4β2 receptor subtypes - involved in the locomotor stimulant effects of nicotine and morphine in mice. This data suggest that cholinergic neurotransmission may be a potential target for developing pharmacotherapeutic strategies to prevent and treat nicotine and/or opioid addiction.
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