Increased neurotransmission within the mesolimbic dopamine system is considered an essential component for the rewarding and dependence producing properties of nicotine. Nicotinic acetylcholine receptors on dopamine containing neurons in the ventral tegmental area are thought to be a prime target for nicotine's stimulatory effects. However, there is no evidence regarding the actions of nicotine on ventral tegmental GABAergic interneurons which play an important modulatory role in mesolimbic dopamine neuronal excitability. In the present study we sought to characterize the effects of nicotine on the activity of both dopamine and non-dopamine neurons in the juvenile rat ventral tegmentum. Extracellular recording techniques in rat brain slices and two methods of drug perfusion were used. Nicotine was found to markedly increase the firing rate of both groups, although the dopamine neuronal response pattern was considerably different and more vigorous than that in the non-dopamine neurons. The nicotine-induced excitations were also reversed by mecamylamine. Furthermore, desensitization to nicotine's stimulatory effects occurred in both neuronal populations, although non-dopamine neurons appeared to desensitize to a greater degree. In fact, the desensitization accompanying sequential uninterrupted applications of nicotine appears to occur at concentrations below that described to produce receptor activation. The low nM concentrations of nicotine used in the present study are comparable to plasma levels of nicotine found after smoking a cigarette or even with passive inhalation of tobacco smoke. Thus, the present results not only confirm that nicotine stimulates the firing rate of ventral tegmental area dopamine neurons, but also that GABAergic neurons may be an important target for nicotine's central nervous system effects. The less robust response in the non-dopamine presumptive GABAergic population and their more pronounced desensitization could lead to disinhibition of dopamine neurons thereby facilitating a more sustained increase in the response of mesolimbic dopamine neurons to nicotine. Copyright (C) 2000 Elsevier Science Inc.
- γ-aminobutyric acid
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