Effect of nicotine pretreatment on striatal dopaminergic system in rats

Rats were pretreated with saline or nicotine (1.5 mg/kg/day) by subcutaneously implanting each animal with an Alzet osmotic minipump for 1 or 14 days. Short-term (1-day) administration of nicotine to rats reduced the stimulatory effect of (+)-amphetamine on locomotor activity. This was correlated with an attenuation in the ability of (+)-amphetamine to stimulate [3H]dopamine formation from [3H]tyrosine in rat striatal slices of these nicotine-treated animals. In long-term (14-day) nicotine-pretreated animals, both the apomorphine- and (+)-amphetamine-induced locomotor activity were potentiated. This behavioral potentiation was associated with an increase in the total number of postsynaptic dopaminergic receptor binding sites in the striatum. The development of striatal dopamine receptor supersensitivity may be caused by a decrease in the rate of dopamine turnover in the striatum.