TOLERANCE TO NICOTINES EFFECTS ON STRIATAL DOPAMINE METABOLISM IN NICOTINE-WITHDRAWN MICE

After 7-week chronic administration of nicotine to mice in their drink ing water, nicotine was withdrawn for 24 h. Acute nicotine challenge ( 1 mg/kg s.c., 60 min) elevated the striatal concentrations of dihydrox yphenylacetic acid (DOPAC) and homovanillic acid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