Effect of nicotine cessation on the central serotonergic systems in mice: involvement of 5-HT(2) receptors.

In the present study, the changes in head twitch responses induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT(2) receptor agonist, following nicotine cessation or during nicotinic receptor antagonist-precipitated withdrawal were investigated in mice. DOI-induced head twitch responses did not change 1.5 h after the final nicotine (0.5 mg/kg per day, s.c. for 7 days) administration, but it increased 24 h later. The increase in head twitch responses induced by nicotine (0.05-1 mg/kg per day) was dose-dependent. The 5-HT turnover ratio (5-HIAA/5-HT) in mouse whole brain was significantly decreased 24 h after the final nicotine administration (0.5 mg/kg per day for 7 days). Mecamylamine, a non-competitive nicotinic receptor antagonist, and dihydro-beta-erythroidine, a competitive alpha(4)beta(2) nicotinic receptor antagonist, precipitated DOI-induced head twitch responses in mice repeatedly treated with nicotine but not with saline, indicating the involvement of alpha(4)beta(2) nicotinic receptors. The present findings suggest cessation of repeated nicotine administration results in increased sensitivity to 5-HT(2) receptor systems and decreased 5-HT turnover, and that these phenomena may be related to the manifestation of nicotine withdrawal symptoms.