Effects of Morphine and its Antagonists on Release of Cerebral Cortical Acetylcholine

Abstract

SEVERAL, studies have shown that the narcotic analgesic morphine and morphine-like compounds reduce the release of acetylcholine (ACh) at peripheral cholinergic junctions^1–3, but there is relatively little evidence that they have a similar action on the central nervous system. Beleslin and Polak⁴ have shown that an intraventricular infusion of morphine in the anaesthetized cat leads to a modest decrease in the release of ACh into the cerebrospinal fluid. The morphine antagonists nalorphine (‘Nalline’) and levallorphan (‘Lorfan’) have been shown to reduce ACh released from the ileum of the guinea-pig, but a comparable action on the release of ACh from the brain has not been demonstrated. There is evidence that the brain contains a system of cholinergic neurones with terminals which project to the cerebral cortex^5,6 and release ACh at the cortical surface⁷. If morphine impaired the release of ACh at the cortical level, and if this action was antagonized by narcotic antagonists such as levallorphan, nalorphine and naloxone, such a reversal cf morphine action by the antagonists could yield important information about the neurohumoral changes associated with the hyperactive state which follows the acute withdrawal of morphine in animals and man⁸. We have therefore investigated the action of morphine on the cortical release of ACh and compared this action with that of morphine antagonists.