Effects of nicotine administration and its withdrawal on plasma corticosterone and brain 5-hydroxyindoles

The effects of nicotine administration and its withdrawal on the levels of brain hydroxyindoles and plasma corticosterone have been studied in the rat. Daily injections of nicotine (0.4 mg/kg s.c.) rapidly induced tolerance to the increase in plasma corticosterone seen in response to acute nicotine. Withdrawal of the drug from chronically treated animals caused a significant increase in plasma corticosterone. Hippocampal 5-hydroxytryptamine (5-HT) was reduced in nicotine-treated rats, significantly so in those treated for more than 20 days. The 5-hydroxyindole acetic acid (5-HIAA) concentration in the hippocampus was also reduced by nicotine although this was not a consistent observation. Hypothalamic 5-hydroxyindoles were not affected by nicotine administration itself, but, if the drug was withdrawn, the concentration of 5-HT was increased after 5 days treatment. The changes in the hypothalamus and hippocampus appeared to be relatively specific since they differed from those seen in the rest of the brain. None of the effects could be related directly to changes in the plasma corticosterone concentration.