Differential effects of nicotine on the activity of substantia nigra and ventral tegmental area dopaminergic neurons in vitro.

Despite resembling each other in many respects, dopaminergic neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) exhibit dissimilar responses to nicotine in vivo. To investigate this in an in vitro model, the acute effects of nicotine on the firing of SNc and VTA neurons were compared in transverse juvenile rat midbrain sections (300-350 microm) using extracellular recording. Levels of nicotine comparable with those encountered in smokers (0.2-1.0 microM, 3 min) not only increased firing rate, but also evoked prolonged irregular firing, as indicated by the increase in the coefficient of variation of discharge frequencies. Pre- and postsynaptic nicotinic cholinergic receptors (nAChRs) were involved, as both effects persisted, although at an attenuated level, in low Ca2+ / high Mg2+. Only the nicotine-induced elevation of firing rate was sensitive to the glutamate receptor antagonists APV and CNQX, implying that enhanced glutamate release and glutamate receptor activation are involved in the effects of nicotine on discharge frequency but not pattern. Furthermore, nicotine (1.0 microM) exerted a greater increase in the firing frequency of VTA neurons relative to SNc neurons, suggesting that the differential effects on the two populations previously reported in vivo were due to a difference in the postsynaptic nAChR response and/or local synaptic circuits. Low concentrations of nicotine can thus profoundly modulate the activity of dopaminergic mesencephalic neurons through a local action within the ventral midbrain in vitro, and, similarly to in vivo conditions, evoke stronger effects in the VTA.