Preclinical and clinical sex differences in the effects of alcohol on measures of brain dopamine: a systematic review.
Study Goal
The researchers aimed to review existing literature on sex differences in the effects of alcohol on brain dopamine measures in animals and individuals with heavy drinking or AUD to inform treatment approaches.
Results Summary
The review found mixed results regarding sex differences in dopamine response to alcohol, with some studies showing greater alcohol-induced dopamine release in females and others showing no differences. Limitations included variability in study designs, timing of alcohol exposure, and measurement techniques.
Population
Animals and individuals with heavy drinking or AUD (1 human study, 9 animal studies).
Effective Dosage
Not specified (varied across included studies).
Duration
Varied across studies (some acute exposure, others longer-term).
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
alcohol challenge | increase | dopamine release | females | - | females had greater alcohol-induced dopamine release than males | #1 |
alcohol challenge | no change | dopamine release | combined AUD/control group or measured days after alcohol exposure | - | showed no sex-related differences | #2 |
prenatal alcohol exposure | increase | prefrontal cortical dopamine D1 receptor availability | prenatal-alcohol-exposed male offspring versus sex-matched air-exposed controls | - | had greater prefrontal cortical dopamine D1 receptor availability | #3 |
prenatal alcohol exposure | increase | striatal dopamine concentration | prenatal-alcohol-exposed female offspring versus sex-matched air-exposed controls | - | had greater striatal dopamine concentration | #4 |
mu-opioid receptor (MOR) regulation of alcohol-induced dopamine release | decrease | alcohol-induced dopamine release | females | - | showed a faster decline in females relative to males | #5 |
mu-opioid receptor (MOR) regulation of alcohol-induced dopamine release | decrease | MOR activity dependence | females | - | females may be less dependent on MOR activity at lower doses of alcohol relative to higher doses | #6 |
INTRODUCTION: Dopamine is involved in reward processing and plays a critical role in the development and progression of alcohol use disorder (AUD). However, little is known about the effect of sex on the relationship between dopamine and alcohol use/AUD. There is a critical need to identify the neurobiological mechanisms that contribute to sex differences in AUD to inform treatment approaches. This study aimed to review existing literature on sex differences in the effects of alcohol on brain dopamine measures in animals and individuals with heavy drinking/AUD. METHODS: A systematic review was conducted using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. PubMed was searched from inception to July 23rd, 2024. RESULTS: Of the 1,412 articles identified, 10 met study criteria (1 human, 9 animal), including in vivo (two positron emission tomography, four microdialysis) and ex vivo (two liquid chromatography, two fast-scan cyclic voltammetry) studies. Six studies included an alcohol challenge; three showed that females had greater alcohol-induced dopamine release than males in the ventral striatum and frontal cortex, while three showed no sex-related differences. Notably, the latter three studies examined sex in a combined AUD/control group or measured dopamine levels days after alcohol exposure. Two studies that examined the effects of prenatal alcohol exposure showed that prenatal-alcohol-exposed male offspring versus sex-matched air-exposed controls had greater prefrontal cortical dopamine D1 receptor availability, and prenatal-alcohol-exposed female offspring versus sex-matched air-exposed controls had greater striatal dopamine concentration. Two studies investigating the mu-opioid receptor (MOR) regulation of alcohol-induced dopamine release showed a faster decline in females relative to males while the other study found females may be less dependent on MOR activity at lower doses of alcohol relative to higher doses. CONCLUSIONS: This systematic review showed mixed results regarding sex differences in brain dopamine measures in alcohol-exposed animals and individuals with AUD, which may arise from differences in the timing, quantity, and duration of alcohol exposure, species, conditions, models, and techniques. More research examining the effect of sex on the relationship between alcohol use and brain dopamine measures is needed to enhance our understanding of AUD development, progression, and treatment in both females and males.