Action of nicotine on accumbens dopamine and attenuation with repeated administration.

The behavioral and physiological effects of repeated nicotine administration are complex; sedation and hypothermia are present early but become attenuated while locomotor activity increases. Maximal blood levels and behavioral changes occur within 10 min of s.c. injection. We examined the effects of 10 nicotine injections (0.8 mg/kg) in 14 days on the levels of brain amines following challenge with either saline or nicotine on the 15th day. Dopamine, DOPAC, HVA, 3-methoxytyramine, norepinephrine, 5-hydroxytyramine, and 5-HIAA were measured in the frontal cortex, olfactory tubercle, nucleus accumbens, caudate-putamen, substantia nigra and ventral tegmental area. Ten minutes after nicotine was given to rats that had previously received only saline the levels of dopamine and its metabolite DOPAC indicated an increase in dopamine turnover in the nucleus accumbens. Of the areas examined the accumbens was the most sensitive to nicotine, with few significant amine changes in other regions. Twenty-four hours after the last nicotine injection the levels of dopamine and its metabolites indicated a sustained decrease in dopamine turnover in the accumbens induced by repeated administration. Following repeated nicotine a nicotine challenge still induced an acute increase in dopamine turnover in the accumbens, but the response was less than in animals not previously given nicotine. The results confirm earlier studies indicating that the accumbens is a major site of nicotine action.