title: MAOA expression predicts vulnerability for alcohol use.
abstract: The role of the monoamines dopamine (DA) and serotonin (5HT) and the monoamine-metabolizing enzyme monoamine oxidase A (MAOA) have been repeatedly implicated in studies of alcohol use and dependence. Genetic investigations of MAOA have yielded conflicting associations between a common polymorphism (MAOA-LPR) and risk for alcohol abuse. The present study provides direct comparison of tissue-specific MAOA expression and the level of alcohol consumption. We analyzed rhesus macaque MAOA (rhMAOA) expression in blood from males before and after 12 months of alcohol self-administration. In addition, nucleus accumbens core (NAc core) and cerebrospinal fluid (CSF) were collected from alcohol access and control (no alcohol access) subjects at the 12-month time point for comparison. The rhMAOA expression level in the blood of alcohol-naive subjects was negatively correlated with subsequent alcohol consumption level. The mRNA expression was independent of rhMAOA-LPR genotype and global promoter methylation. After 12 months of alcohol use, blood rhMAOA expression had decreased in an alcohol dose-dependent manner. Also after 12 months, rhMAOA expression in the NAc core was significantly lower in the heavy drinkers, as compared with control subjects. The CSF measured higher levels of DA and lower DOPAC/DA ratios among the heavy drinkers at the same time point. These results provide novel evidence that blood MAOA expression predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the blood and NAc core. Together, the findings suggest a mechanistic link between dampened MAOA expression, elevated DA and alcohol abuse.
authors.affiliation: Department of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
authors.forename: R
authors.initials: R
authors.lastname: Cervera-Juanes
authors.affiliation: Department of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Wilhem
authors.affiliation: Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, USA.
authors.forename: B
authors.initials: B
authors.lastname: Park
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Lee
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Locke
authors.affiliation: Department of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
authors.forename: C
authors.initials: C
authors.lastname: Helms
authors.affiliation: Department of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gonzales
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.|Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: G
authors.initials: G
authors.lastname: Wand
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Jones
authors.affiliation: Department of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Grant
authors.affiliation: Department of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
authors.forename: B
authors.identifier: http://orcid.org/0000-0002-6992-3538
authors.initials: B
authors.lastname: Ferguson
mesh_terms: D000428:Alcohol Drinking / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism; D000437:Alcoholism / Q000097:blood / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000235:genetics; D000483:Alleles; D000818:Animals; D016022:Case-Control Studies; D004298:Dopamine / Q000134:cerebrospinal fluid / Q000378:metabolism; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D008253:Macaca mulatta; D008297:Male; D008995:Monoamine Oxidase / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012701:Serotonin / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D012701:Serotonin; D008995:Monoamine Oxidase; D004298:Dopamine