Sex Differences in the Neurobiology of Alcohol Use Disorder

Abstract

Sex differences may play a critical role in modulating how chronic or heavy alcohol use impacts the brain to cause the development of alcohol use disorder (AUD). AUD is a multifaceted and complex disorder driven by changes in key neurobiological structures that regulate executive function, memory, and stress. A three-stage framework of addiction (binge/intoxication; withdrawal/negative affect; preoccupation/anticipation) has been useful for conceptualizing the complexities of AUD and other addictions. Initially, alcohol drinking causes short-term effects that involve signaling mediated by several neurotransmitter systems such as dopamine, corticotropin releasing factor, and glutamate. With continued intoxication, alcohol leads to dysfunctional behaviors that are thought to be due in part to alterations of these and other neurotransmitter systems, along with alterations in neural pathways connecting prefrontal and limbic structures. Using the three-stage framework, this review highlights examples of research examining sex differences in drinking and differential modulation of neural systems contributing to the development of AUD. New insights addressing the role of sex differences in AUD are advancing the field forward by uncovering the complex interactions that mediate vulnerability.

Shortening Time for Alcohol Access Drives Up Front-Loading Behavior, Bringing Consumption in Male Rats to the Level of Females

“…3.1 Front-loading drives sex differences in voluntary alcohol intake and is greatest when testing occurs later in the dark cycle Sex differences in alcohol consumption emerge by adulthood in rodents, with females drinking more than males (Juárez and De Tomasi, 1999;Randall et al, 2017); for review see (Flores-Bonilla and Richardson, 2020). As expected, the average of total alcohol intake (g/kg) within 30-minute sessions was higher in adult female rats compared to males (Fig.…”

“…The factors motivating drinking and the health consequences of heavy alcohol use can differ with sex (Flores-Bonilla and Richardson, 2020). Adolescent girls report drinking alcohol as a coping mechanism to alleviate depression and psychological distress because of its acute anxiety-reducing properties, while drinking in adolescent boys tends to relate more to risk-taking and impulsive behaviors (Bekman et al, 2013;Kuntsche and Müller, 2012).…”

“…These negative consequences are exacerbated by excessive patterns of compulsive drinking; e.g., binge drinking (Fede et al, 2020;Kvamme et al, 2016;Mashhoon et al, 2014;National Institute on Alcohol Abuse and Alcoholism, 2004); reviewed in (Becker et al, 2012;George et al, 2014;Koob, 2013;Mason, 2017;Peltier et al, 2019). Binge drinking is considered the first of the three stages of addiction: Binge/Intoxication, Negative Affect/Withdrawal, and Preoccupation/Anticipation, with evidence of sex differences being reported in all three stages, reviewed in (Flores-Bonilla and Richardson, 2020). While the prevalence of binge drinking is higher in men (33%) than women (17%), women experience greater mental health instability (17.3% vs. 8.6%) and worse mental health consequences (11.2% vs. 6.3%) compared to men (Patrick et al, 2020;Substance Abuse and Mental Health Services Administration, 2014).…”

Impact of Alcohol Abuse on Susceptibility to Rare Neurodegenerative Diseases

“…In translational work, chronic alcohol is also associated with changes in the transcriptomic profile of the oxidative stress pathway (Bogenpohl et al, 2019). Prenatal alcohol has even more severe effects on the transcription of multiple targets within pathways that mediate neuronal migration and synaptic function (Fischer et al, 2019).…”

From the Editors

“…In “Sex Differences in the Neurobiology of Alcohol Use Disorder,” Flores-Bonilla and Richardson explore preclinical and human research on neural differences using a three-stage framework of addiction. 9 Specifically, they examine how neurobiological differences contribute to initial development of binge/intoxicated drinking, the transition into withdrawal, negative affect and dysfunctional behaviors associated with continued heavy drinking, and finally development of preoccupation with or craving for alcohol and compulsive drinking, and relapse. 9 …”