Muscarine depolarizes rat substantia nigra zona compacta and ventral tegmental neurons in vitro through M1-like receptors

Intracellular recordings were made from presumed dopamine-containing neurons in slices of rat mesencephalon. Muscarine (3-100 μM) 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 μM) with an estimated K(D) 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 (10 mM) solution. It is concluded that muscarinic excitation of dopaminergic neurons is mediated by M₁-like receptors.