In order to determine whether ethanol antagonizes central eholinergic pathways, the effects of anticholinesterase and anticholinergic drugs on ethanol-induced sleeping time and death were studied in mice. Physostigmine, in an optimum dose of 0.1 mg/kg given at the same time as 4.5 g/kg ethanol, significantly shortened sleeping time when compared to controls given saline and ethanol. A physostigmine dose of 0.5 mg/kg combined with the sublethal dose of ethanol produced death in a large percentage of mice. Studies with neostigmine, atropine, and methyl atropine nitrate provided evidence that the chollnergic-ethanol antagonism of sleeping time is a central phenomenon, whereas the cholinergic-ethanol lethality is a peripheral phenomenon. The apparent central cholinergic antagonism of ethanol sleeping time strongly suggests that at least part of ethanol's central depressant action may be concerned with inhibition of acetylcholine release or function.The site and mechanism of action of ethanol (ETOH) have not been definitely established in spite of many attempts to do so. Both the brain stem reticular activating system and cerebral cortex have been implicated as sites of action for ETOH [1], and neurophysiologically, it seems likely that ETOH as a depressant must block the function of central neurons either in the reticular activating system or cortex or both. Investigators have suggested numerous ways in which this block of function could occur, including blockade of neurohumoral release. Most neurohumoral studies with ETOH have been concerned with serotonin, norepinephrine, dopamine, and gamma-aminobutyric acid, and although studies on the release and uptake of acetylcholine during the action of many depressants have been performed, similar data on ETOH's central effects on acetylcholine activity are sparse. Studies on the respiration of brain cortex tissue in vitro indicate that ETOH depolarizes and synergizes with acetylcholine to increase tissue respiration after an electrical stimulation [2]. However, more recent work has suggested that ETOH may inhibit acetylcholine release at central cholinergic synapses [3,4]. ROSENFELD [5] has shown an increase in mortality and sleeping time after ETOH and exogenous monoamines in mice. He postulated that a causal relationship exists between the neuropharmacological effects of ETOH in narcotic doses and its influence on the metabolism of one or more endogenous aromatic monoamines present in the central nervous system. Since ROSENFELD did not implicate monoamine transmission as being involved in ETOH's action in the central nervous system and since the reticular activating system and cerebral cortex have been found to be at least partly cholinergic [6,7,8], it is tempting to speculate that ETOH may inhibit the release of acetylcholine in one or both of these structures.In an attempt to gain evidence toward the hypothesis that ETOH affects acetylcholine release or function in the brain, the effects of cholinesterase inhibitors and cholinergic blocking agents on ETOH-ind...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.