Once weekly administration of nicotine produces long-lasting locomotor sensitization in rats via a nicotinic receptor-mediated mechanism

Rationale: Chronic nicotine administration results in dynamic changes in ne uronal function, expressed as behavioral sensitization in animals and addic tion in smokers. Objectives: The present study was undertaken to determine whether once-weekly nicotine injection produces sensitization to the locomo tor-activating properties of nicotine as a result of nicotinic receptor act ivation. Methods: Once weekly for 6 weeks, rats were administered (s.c.) tw o saline injections or saline and nicotine (0.35 mg/kg), and locomotor acti vity was monitored. Rats remained in the home cage for 21 days, and subsequ ently were injected with the appropriate treatment to determine whether sen sitization persisted. Rats were also injected with saline or mecamylamine ( 1.2 mg/kg) followed by saline or nicotine once weekly for 6 weeks to determ ine the effect of mecamylamine and whether it inhibited nicotine-induced hy peractivity. A separate group was injected with saline and nicotine once we ekly for 4 weeks; on week 5, mecamylamine and nicotine were administered to determine whether mecamylamine inhibited the expression of sensitization. Separate groups were injected with mecamylamine and nicotine once weekly fo r 5 weeks or 6 weeks; on week 6 or week 9, respectively, saline and nicotin e were injected to determine whether mecamylamine inhibited the initiation of sensitization. Results: Sensitization to the locomotor-activating proper ties of nicotine developed following four nicotine injections across a 28-d ay period and persisted following 21 days of no drug treatment. Mecamylamin e did not alter activity but attenuated both the initiation and expression of sensitization. Conclusions: Nicotinic receptor activation following once -weekly nicotine administration produces long-lasting behavioral sensitizat ion, suggesting that even infrequent nicotine exposure initiates neuroadapt ive processes associated with nicotine addiction.