Muscarinic receptors mediate attenuation of extracellular acetylcholine levels in rat cerebral cortex after cholinesterase inhibition.

Muscarinic autoregulation of extracellular acetylcholine levels was investigated by microdialysis in the cerebral cortex of freely moving rats under basal conditions as well as following systemic administration of a reversible cholinesterase inhibitor. Atropine (2.2 mg/kg s.c. or 0.2 microM via the dialysis probe) did not affect basal extracellular acetylcholine levels in the cerebral cortex. However, it did potentiate the elevation of extracellular acetylcholine levels produced by a dose of systemic heptylphysostigmine which inhibited 25% of cortical and 40% of plasma cholinesterase activity. These observations suggest that the extracellular concentration of acetylcholine following moderate acetylcholinesterase inhibition is regulated through muscarinic receptors.