Ry. Yin et Ed. French, A comparison of the effects of nicotine on dopamine and non-dopamine neurons in the rat ventral tegmental area: An in vitro electrophysiological study, BRAIN RES B, 51(6), 2000, pp. 507-514
Increased neurotransmission within the mesolimbic dopamine system is consid
ered an essential component for the rewarding and dependence producing prop
erties of nicotine. Nicotinic acetylcholine receptors on dopamine containin
g neurons in the ventral tegmental area are thought to be a prime target fo
r nicotine's stimulatory effects, However, there is no evidence regarding t
he actions of nicotine on ventral tegmental GABAergic interneurons which pl
ay an important modulatory role in mesolimbic dopamine neuronal excitabilit
y. In the present study we sought to characterize the effects of nicotine o
n the activity of both dopamine and non-dopamine neurons in the juvenile ra
t ventral tegmentum, Extracellular recording techniques in rat brain slices
and two methods of drug perfusion were used. Nicotine was found to markedl
y increase the firing rate of both groups, although the dopamine neuronal r
esponse pattern was considerably different and more vigorous than that in t
he non-dopamine neurons. The nicotine-induced excitations were also reverse
d by mecamylamine, Furthermore, desensitization to nicotine's stimulatory e
ffects 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 o
ccur at concentrations below that described to produce receptor activation.
The low nM concentrations of nicotine used in the present study are compar
able to plasma levels of nicotine found after smoking a cigarette or even w
ith 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 targ
et for nicotine's central nervous system effects. The less robust response
in the non-dopamine presumptive GABAergic population and their more pronoun
ced desensitization could lead to disinhibition of dopamine neurons thereby
facilitating a more sustained increase in the response of mesolimbic dopam
ine neurons to nicotine. (C) 2000 Elsevier Science Inc.