Muscarinic agonist-mediated induction of long-term potentiation in rat cerebral cortex.

A long-lasting potentiation (usually following an initial short depression) of neuronal evoked responses was induced in neurons of rat sensorimotor cortex after a single application of the muscarinic agonists, oxotremorine, McN-A-343, or oxotremorine-M. The potentiation was characterized as being of slow onset (several minutes), progressive development, long-lasting (for as long as two hours), and was evident for both glutamate- and acetylcholine-evoked neuronal discharges. Potentiation was manifested as an increase in the frequency and duration of the evoked neuronal discharges, in a dose-dependent fashion. Blockade could be achieved if a muscarinic antagonist (atropine, pirenzepine or gallamine) was applied prior to, but not after, development of the long-lasting potentiation. These results suggest that certain muscarinic agonists may be useful in reducing the memory deficits of patients with Alzheimer's disease.