Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation.

M Bendre,K W Nilsson,I Nylander,E Comasco

doi:10.1038/tp.2015.186

Abstract

Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption affect Maoa expression in stress- and reward-related brain regions in the rat. Outbred Wistar rats were exposed to rearing conditions associated with stress (prolonged maternal separation) or no stress during early life, and given free choice between alcohol and/or water in adulthood. Transcript levels of Maoa were assessed in the ventral tegmental area, nucleus accumbens (NAc), medial prefrontal cortex, cingulate cortex, amygdala and dorsal striatum (DS). Blood was collected to assess corticosterone levels. After alcohol consumption, lower blood corticosterone and Maoa expression in the NAc and DS were found in rats exposed to early life stress compared with control rats. An interaction between early life stress and voluntary alcohol intake was found in the NAc. Alcohol intake before death correlated negatively with Maoa expression in DS in high alcohol-drinking rats exposed to early life stress. Maoa expression is sensitive to adulthood voluntary alcohol consumption in the presence of early life stress in outbred rats. These findings add knowledge of the molecular basis of the previously reported associations between early life stress, MAOA and susceptibility to alcohol misuse.

Highlights

Alcohol misuse is a major problem with health, economic and social consequences.[1]
Early life stress, voluntary alcohol consumption and Maoa expression The effect of voluntary episodic alcohol consumption on Maoa expression was examined in stress- and reward-related key brain regions in young adults outbred male Wistar rats subjected to early life stress (MS360) or no stress
Lower Maoa expression was found in nucleus accumbens (NAc) and dorsal striatum (DS) of ethanol drinking maternal separation for 360 min (MS360) rats

Summary

Introduction

Alcohol misuse is a major problem with health, economic and social consequences.[1] Alcohol is frequently consumed for its pleasurable and euphoric effects, that is, positive reinforcing effects, and for its sedative and stress relieving effects, that is, negative reinforcing effects.[2,3] The progression from controlled drinking to compulsive drinking is crucial for the development of alcohol use disorder (AUD) and involves several neuronal circuits.[3]. A regulatory role is played by serotonergic neurons in this pathway in mediating the rewarding and reinforcing effects of alcohol,[9,10] as well as by noradrenergic neurons in mediating the effects of negative emotions that arises due to withdrawal of alcohol and stress-related relapse.[11] Monoaminergic neurotransmitters play a key role in mediating both the acute and chronic effects of alcohol. Long-term alcohol exposure induces changes in expression of monoaminergic genes in mesocorticolimbic brain regions of rats.[17,18]

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