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 required to maintain half-maximal response rates with animals responding in rate-frequency threshold tests. Under these conditions, nicotine induced an increase in the total number of self-stimulation responses per session, but had no statistically significant effects on the maximal response rate. These effects of nicotine were observed by the second day of administration of this drug. Acute injections of the D-2-like dopamine receptor antagonist haloperidol (0.03 mg kg(-1) SC) and of the nicotinic acetylcholine receptor antagonist mecamylamine (1 mg kg(-1) SC) attenuated the effects of nicotine, indicating that the observed effects involve stimulation of D-2-like dopamine receptors as a result of nicotinic receptor activation. The muscarinic acetylcholine receptor antagonist scopolamine (3 mg kg(-1) SC) and the serotonin 5-HT3 receptor antagonist ondansetron (0.01 and 0.1 mg kg(-1) SC) did not alter the effects of nicotine. The results of this study indicate that repeated daily administration of (-)-nicotine increases the rewarding effects of electrical self-stimulation of the ventral tegmental area. These data are consistent with the proposal that repeated daily injections of nicotine positively effect a mesolimbic dopaminergic substrate of reward.