Elevated monoamine oxidase A activity and protein levels in rodent brain during acute withdrawal after chronic intermittent ethanol vapor exposure

Abstract Background A key component of alcohol dependence (AD), a severe form of alcohol use disorder, is the negative emotional state during withdrawal. Monoamine oxidase A (MAO-A) is an important enzyme that metabolizes monoamines and creates oxidative stress. Elevations in MAO-A level, especially in the prefrontal and anterior cingulate cortex (PFC and ACC), are associated with low mood states, including the dysphoria of early alcohol withdrawal in humans. The aim of the present study was to determine whether chronic alcohol vapor exposure causes an upregulation of MAO-A activity or level in the PFC and ACC of rodents during acute withdrawal. Methods Sprague-Dawley rats were exposed to ethanol vapor or control condition for 17 h per day for 8 weeks. MAO-A activity and protein levels were measured immediately after exposure, acute withdrawal (24 h), protracted withdrawal (4 day), and protracted abstinence (3 weeks) (n = 16/group; 8 alcohol exposed, 8 control). Results Chronic ethanol vapor exposure significantly elevated MAO-A activity and protein levels in the PFC and ACC at 24-h withdrawal (multivariate analysis of variance (MANOVA), activity: F 2,13  = 3.82, p = .05, protein: F 2,13  = 5.13, p = .02). There were no significant changes in MAO-A level or activity at other timepoints. Conclusions The results of this study suggest a causal relationship between acute alcohol withdrawal and elevated MAO-A levels and activity, clarifying the observation of greater MAO-A binding in human alcohol withdrawal. This has important implications for developing methods of targeting MAO-A and/or sequelae of its dysregulation in alcohol dependence.