Tolerance to nicotine's effects on striatal dopamine metabolism in nicotine-withdrawn mice

After 7-week chronic administration of nicotine to mice in their drinking water, nicotine was withdrawn for 24 h. Acute nicotine challenge (1 mg/kg s.c., 60 min) elevated the striatal concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and decreased the concentration of 3-methoxytyramine significantly less in the mice withdrawn for 24 h from nicotine than in the control mice which had been drinking tap water under identical conditions for 7 weeks. Neither withdrawal nor the acute nicotine challenge altered the striatal dopamine concentration. No alterations were found in the density or affinity of the specific binding of [ 3H]SCH 23390 or [ 3H]spiperone to striatal membrane homogenates during nicotine treatment or after its withdrawal. Thus, our results show that tolerance to the acute effects of nicotine on striatal dopamine metabolism can be induced by administering nicotine to mice in the drinking water. However, neither chronic nicotine treatment nor its withdrawal seem to affect dopamine D 1 and D 2 receptors in the striatum.