Enkephalin effects on release of brain acetylcholine

Abstract

MORPHINE and other narcotic analgesics depress the spontaneous release of acetylcholine (ACh) from the rat cerebral cortex in vivo^1,2. The effect of these agents on the central release of ACh, like their inhibitory effects on the peripheral release of ACh in the guinea pig ileum, is stereospecific³ and can be fully antagonised by naloxone⁴. It is well recognised that the endogenous opiate peptides, enkephalins^5,6 and endorphins⁷, depress the output of ACh from the electrically stimulated guinea pig ileum by a specific action on opiate receptors. This suggests that in the central nervous system endogenous opiates may exert a significant influence on the release of ACh. We have examined the effects of two enkephalins, methionine-enkephalin (Met-enkephalin) and leucine-enkephalin (Leu-enkephalin) on the cortical release of ACh in vivo following intraventricular injections. Our observations show that natural enkephalins may interact with opiate receptors in the brain to modulate the release of ACh from the cholinergic neurones.