NICOTINE-INDUCED DECREASES IN VTA ELECTRICAL SELF-STIMULATION THRESHOLDS - BLOCKADE BY HALOPERIDOL AND MECAMYLAMINE BUT NOT SCOPOLAMINE OR ONDANSETRON

The effects of repeated daily injections of (-)-nicotine (+) hydrogen tartrate (mg kg(-1) SC) on electrical self-stimulation of the ventral tegmental area were investigated. Nicotine reduced the frequency requi red to maintain half-maximal response rates with animals responding in rate-frequency threshold tests. Under these conditions, nicotine indu ced an increase in the total number of self-stimulation responses per session, but had no statistically significant effects on the maximal r esponse rate. These effects of nicotine were observed by the second da y of administration of this drug. Acute injections of the D-2-like dop amine receptor antagonist haloperidol (0.03 mg kg(-1) SC) and of the n icotinic acetylcholine receptor antagonist mecamylamine (1 mg kg(-1) S C) attenuated the effects of nicotine, indicating that the observed ef fects involve stimulation of D-2-like dopamine receptors as a result o f nicotinic receptor activation. The muscarinic acetylcholine receptor antagonist scopolamine (3 mg kg(-1) SC) and the serotonin 5-HT3 recep tor antagonist ondansetron (0.01 and 0.1 mg kg(-1) SC) did not alter t he effects of nicotine. The results of this study indicate that repeat ed daily administration of (-)-nicotine increases the rewarding effect s of electrical self-stimulation of the ventral tegmental area. These data are consistent with the proposal that repeated daily injections o f nicotine positively effect a mesolimbic dopaminergic substrate of re ward.