Cross-Species Alterations in Synaptic Dopamine Regulation After Chronic Alcohol Exposure

Abstract

Alcohol use disorders are a leading public health concern, engendering enormous costs in terms of both economic loss and human suffering. These disorders are characterized by compulsive and excessive alcohol use, as well as negative affect and alcohol craving during abstinence. Extensive research has implicated the dopamine system in both the acute pharmacological effects of alcohol and the symptomology of alcohol use disorders that develop after extended alcohol use. Preclinical research has shed light on many mechanisms by which chronic alcohol exposure dysregulates the dopamine system. However, many of the findings are inconsistent across experimental parameters such as alcohol exposure length, route of administration, and model organism. We propose that the dopaminergic alterations driving the core symptomology of alcohol use disorders are likely to be relatively stable across experimental settings. Recent work has been aimed at using multiple model organisms (mouse, rat, monkey) across various alcohol exposure procedures to search for commonalities. Here, we review recent advances in our understanding of the effects of chronic alcohol use on the dopamine system by highlighting findings that are consistent across experimental setting and species.

Long-term alcohol consumption alters dorsal striatal dopamine release and regulation by D2 dopamine receptors in rhesus macaques

“…Thus, any apparent dopamine uptake differences in the male macaque groups presented here are a function of faster clearance times due to decreased dopamine release and not faster dopamine clearance rates per se. Interestingly, across multiple studies, chronic alcohol use resulted in enhanced dopamine uptake rates, though this effect has been found to vary between species and striatal subregions (for review, see [ 10 ]). Nonetheless, our observed adaptations in dopamine uptake may contribute to the apparent changes in dopamine release following long-term alcohol consumption.…”

“…The role of dopamine in AUD is complex and has been reviewed in detail elsewhere [ 10 – 13 ]. Briefly, acute alcohol increases dopamine release across the striatum [ 14 ] primarily due to increased firing of midbrain dopaminergic neurons, an effect that may underlie the initial reinforcing properties of alcohol.…”

Sex Differences in the Neurobiology of Alcohol Use Disorder

“…Prolonged heavy alcohol use leads to a state of a constant preoccupation with alcohol and compulsive drinking despite negative consequences. 88 , 101 , 102 This craving can continue into abstinence for months or years, making it difficult to abstain from alcohol altogether or to shift to a healthier level of drinking. 103 …”

Researching Mitigation of Alcohol Binge Drinking in Polydrug Abuse: KCNK13 and RASGRF2 Gene(s) Risk Polymorphisms Coupled with Genetic Addiction Risk Severity (GARS) Guiding Precision Pro-Dopamine Regulation

“…Therefore, the identification of these polymorphisms is worthy of investigation. Furthermore, impairments caused by binge drinking or chronic alcohol intake, via these known mechanisms, support the idea of “dopamine homeostasis” [ 53 , 54 , 55 ] and its impairments in AUD.…”