Muscarinic agonist oxotremorine-M-induced long-term depression in rat cerebral cortex

A long-lasting depression (LTD) of neuronal-evoked responses was induced in a dose-dependent fashion in neurons of rat sensorimotor cortex by a brief application of the muscarinic agonist oxotremorine-M. The depression was characterized as being of rapid onset (within 30 seconds), long duration (up to 40 minutes), and was evident for both glutamate- and acetylcholine-evoked discharges. Antagonism could be achieved by application of the nonspecific muscarinic antagonist atropine, and with the M2 antagonists gallamine or methoctramine. The M1 antagonist pirenzepine displayed only a weak effect. LTD could also be induced by the muscarinic agonists, oxotremorine and McN-A-343, but their potencies were lower than that of oxotremorine-M. Oxotremorine-M may be a useful tool for studies of long-term changes in synaptic efficacy.