In vitro modulation of the firing rate of dopamine neurons in the rat substantia nigra pars compacta and the ventral tegmental area by antipsychotic drugs

An in vitro experimental midbrain slice preparation is described which allo ws simultaneous extracellular recordings of the (spontaneous) electrical ac tivity of dopamine neurons in the rat substantia nigra (SN) and the ventral tegmental area (VTA). Under identical in vitro circumstances the mean firi ng frequency of the SN dopamine neurons was higher than that of the VTA dop amine neurons (2.1 vs. 1.4 Hz). With this slice preparation, modulation of the electrical activity of SN and VTA dopamine neurons by (new) drugs can b e quickly determined. Experiments with the selective D, receptor agonist qu inpirole and the selective D, receptor antagonist (-)-sulpiride indicated t hat dopamine neurons in the SN and VTA hardly differ in their pharmacologic al properties for the D-2-like (auto)receptor. (-)-Sulpiride and to a lesse r extent risperidone induced a small increase in firing rate in SN and VTA neurons, which was reversible upon wash-out. Olanzapine-induced increase in firing rate was persistent in SN and VTA neurons, whereas the clozapine-in duced increase in firing rate was only completely recovered upon wash-out i n SN neurons. The difference in firing rates of SN and VTA dopamine neurons could have consequences for the effectiveness of dopaminergic drugs acting at the D-2-like dopamine (auto)receptor on these neurons. (C) 2001 Elsevie r Science Ltd. All rights reserved.