Muscarinic receptor-mediated inhibition of dopaminergic excitatory input to caudate neurons from the substantia nigra.

Abstract

Microiontophoretic studies using rats anesthetized with chloral hydrate were performed to elucidate the relationship between the striatal cholinergic system and nigrostriatal dopaminergic system. Iontophoretic application of carbachol inhibited the spikes elicited by substantia nigra (SN) stimulation in 21 of 24 caudate neurons in which the spikes induced by SN stimulation were inhibited by microiontophoretically applied domperidone, a dopamine D-2 receptor antagonist. This inhibitory effect was completely blocked by atropine, although the spike generation induced by SN stimulation remained unaffected by the drug. However, carbachol did not affect the glutamate-induced firing of the caudate neurons of which the spikes induced by SN stimulation were inhibited by application of both domperidone and carbachol. Furthermore, carbachol had inhibitory effects on the spikes induced by SN stimulation even after the systemic application of bicuculline. In contrast, in 17 of 24 caudate neurons in which the spikes induced by SN stimulation were not affected by domperidone, carbachol did not inhibit the spikes induced by SN stimulation. These results suggest that the muscarinic receptors located on the SN-derived dopaminergic nerve terminals mainly play a role in inhibiting inputs from the SN to the caudate neurons, probably by reducing the release of dopamine from the nerve terminals.