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 allows simultaneous extracellular recordings of the (spontaneous) electrical activity of dopamine neurons in the rat substantia nigra (SN) and the ventral tegmental area (VTA). Under identical in vitro circumstances the mean firing frequency of the SN dopamine neurons was higher than that of the VTA dopamine neurons (2.1 vs. 1.4Hz). With this slice preparation, modulation of the electrical activity of SN and VTA dopamine neurons by (new) drugs can be quickly determined. Experiments with the selective D2 receptor agonist quinpirole and the selective D2 receptor antagonist (-)-sulpiride indicated that dopamine neurons in the SN and VTA hardly differ in their pharmacological properties for the D2-like (auto)receptor. (-)-Sulpiride and to a lesser 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-induced increase in firing rate was only completely recovered upon wash-out in 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 D2-like dopamine (auto)receptor on these neurons.