The effect of topically applied atropine on resting and evoked cortical acetylcholine release.

1. Cortical acetylcholine (ACh) output was measured in cats anaesthetized either with Dial compound (0.6 ml./kg) or with halothane-N(2)O. ACh output was found to be 1.67 ng/cm(2).min under Dial anaesthesia, and 0.30 ng/cm(2).min under halothane-N(2)O.2. Addition of atropine sulphate (1 mug/ml.) to the collection fluid increased ACh output fourfold under Dial anaesthesia but had no effect under halothane-N(2)O anaesthesia.3. Isolation of the cortex, lesions in the mesencephalon and topical application of tetrodotoxin (TTX) reduced ACh output under Dial anaesthesia to about 0.8 ng/cm(2).min. The effect of atropine on ACh output was somewhat reduced by isolation and completely abolished by mesencephalic lesions or TTX.4. ACh release evoked by reticular formation stimulation under halothane-N(2)O anaesthesia was increased fourfold by atropine but evoked release due to direct stimulation of the cortex was increased only twofold.5. ACh release due to depolarization of the cortex with KCl was not increased by atropine.6. Dihydro-beta-erythroidine (DHE) or D-tubocurarine failed to affect ACh output even in a concentration of 100 mug/ml.7. It is concluded that atropine does not increase spontaneous ACh release and only ACh release evoked by trans-synaptic stimulation of cholinergic neurones is potentiated by atropine.8. These findings are fully consistent with the hypothesis that atropine increases ACh output by blocking cortical cholinergic synapses which are a part of a circuit inhibiting cholinergic neurones.