Carbachol produced an approximately 2-fold stimulation, with respect to basal, of [H-3]inositol monophosphate ([H-3]IP1) accumulation in microdissected slices of rat substantia nigra pars reticulata (SNr), measured as a percentage of [H-3]inositol incorporation. The response to carbachol was inhibited by 75+/-7% by 1 muM pirenzepine, consistent with a muscarinic M1 receptor-mediated response. Carbachol-induced [H-3]IP1 accumulation was not reduced by pretreatment of the SNr slices with NMDA, in contrast to the 85% inhibition observed in striatal slices. The results suggest that measurement of carbachol-induced phosphoinositide hydrolysis may be a feasible approach for studying muscarinic M1 receptor function in slices of SNr.