Intracellular recordings were made from presumed dopamine-containing neurons in slices of rat mesencephalon. Muscanne (3-1 00 tM) increased the rate of spontaneous action potentials; it also caused a membrane depolarization and, in voltage-clamp, an inward current. Concentration-effect curves to muscarine were shifted rightwards by pirenzepine(0.03-1 M) with an estimated K0 of 14 nM. The inward current caused by muscarine was voltage-dependent. Between about-50 and--65 mV it was associated with a decrease in membrane conductance, but between-70 and-110 mV it was unaccompanied by any change in membrane conductance. Muscarine was without effect on the action potential afterhyperpolarization, or on a slowly developing inward current evoked by step hyperpolarizations of up to 20 mV from-45 mV. Muscarinic depolarizations or inward currents were reduced reversibly or abolished by a low calcium (0.25 mM)/high magnesium(1 0 mM) solution. It is concluded that muscarinic excitation of dopaminergic neurons is mediated by M1-like receptors.

The presence of acetylcholinesterase(Butcher, 1977) and of neuropil exhibiting choline acetyltransferase immunoreactivity (Beninato and Spencer, 1988) provides some anatomical evidence for a cholinergic innervation of the dopamine-containing neurons of the SNC and the VTA. There are no cholinergic neurons within the SNC or VTA(Mesulam et al., 1983), but it has been proposed that there is a projection to the SNC from