MUSCARINIC RECEPTOR MODULATION OF ACETYLCHOLINE-RELEASE FROM RAT CEREBRAL-CORTEX AND HIPPOCAMPUS

An attempt to identify the muscarinic receptor subtypes involved in pr esynaptic modulation of acetylcholine (ACh) release from cortical and hippocampal slices was made by means of several muscarinic antagonists . Cortical and hippocampal slices prepared from adult rats were superf used with Krebs solution containing physostigmine; ACh content of the superfusate at rest and after electrical stimulation (I Hz) was quanti fied by high performance liquid chromatography. The antagonists were a dded to the Krebs at the concentration of 1 mu M. ACh release at rest was enhanced only in the cortex by rbonyl}-6H-pyrido[2,3-b](1,4)-benzo diazepine-6-one (AFDX384), an M2/M4 selective antagonist. The evoked A Ch release from the cerebral cortex was significantly increased by AFD X384, methoctramine, pirenzepine, M2/M4, M2 and M1 selective antagonis ts, respectively, and scopolamine. This finding suggests that M1, M2 a nd M4 presynaptic receptor subtypes could regulate evoked ACh release in the cortex. In hippocampal slices, the evoked ACh release was enhan ced by AFDX384, pirenzepine and scopolamine but not by methoctramine. In this region ACh release seems therefore regulated only by M1 and M4 receptor subtypes. The M3 antagonist (+/-)-p-fluorohexahydro-sila-dif enidol hydrochloride did not affect ACh release.