Antagonism of morphine action on brain acetylcholine release by methylxanthines and calcium

The inhibitory effect of morphine on the release of acetylcholine (ACh) from the rat cerebral cortex was antagonized by theophylline, caffeine and 3-isobutyl-1-methylxanthine (IBMX). Theophylline antagonism of morphine action was dose related and this agent failed to influence a comparable action of chlorpromazine on the release of ACh. Intraventricular injection of calcium also antagonized the anti-release effect of morphine. Neither methylxanthines nor calcium modified the spontaneous release of ACh in the absence of morphine. It is suggested that methylxanthine antagonism of morphine action is selective and that it could be related to the ability of methylxanthines to mobilize bound calcium.