The Dopamine System in Mediating Alcohol Effects in Humans

Krystal J et al., The vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia. Conversely, there are also high rates of alcohol-related disorders in psychiatric patients, particularly in those with bipolar disorder and depression when compared to the general population 19, 20. Genetic susceptibility linked to thiamine transporter genes may be involved in the development of WKS in vulnerable patients. These alkaloid compounds have been suggested to be responsible for the physiological effects of alcohol as well as the manifestation of the behavioural aspects of alcohol-related disorders. Opioid systems involving endogenous opioids (endorphins, enkephalins and dynorphins) influence drinking behaviour via interaction with the mesolimbic system.

Warm colors indicate increased connectivity following dopamine depletion, whereas cool colors indicate decreased connectivity following dopamine depletion. We assessed selective attention capture using a dot-probe task modified from our previous studies assessing AB toward smoking cues in cigarette smokers 62, 63 (See Supplementary Materials). Faster response times (RT) in trials in which the target was congruent with the alcohol image versus the neutral image indicates AB toward alcohol-related cues via selective attention capture. Alcohol is one the most widely used and abused drugs in the world and the number of annual alcohol-attributed deaths exceeds 3 million 1. In the United States of America, alcohol use disorder (AUD) accounts for annual economic losses of ~$250 billion 2 and ~88,000 deaths 3.

How Does Alcohol Affect Your Brain?

Blackouts are gaps in a person’s memory of events that occurred while they were intoxicated. These gaps happen when a person drinks enough alcohol that it temporarily blocks the transfer of memories from short-term to long-term storage—known as memory consolidation—in a brain area called the hippocampus. In short, alcohol use during adolescence can interfere with structural and functional brain development and increase the risk for AUD not only during adolescence but also into adulthood. To help clinicians prevent alcohol-related harm in adolescents, NIAAA developed a clinician’s guide that provides a quick and effective screening tool (see Resources below).

Short-term effects

This study showed that microinjection of either quinpirole or quinelorane, into the anterior part of the VTA dose‐dependently decreased alcohol, but not sucrose, intake in alcohol‐preferring rats 142. In support are the data showing that local administration of cabergoline into the VTA reduced alcohol‐seeking behaviour in rats 170. These data are contradictory to the findings showing that the dopamine D2 receptor antagonist into the anterior VTA did not alter alcohol intake in high‐alcohol‐preferring rats 142. Therefore, mechanisms regulating alcohol reinforcement might be different in selectively breed high alcohol‐consuming rats compared to outbreed rats, and this should be investigated in more detail.

Alcohol Use Disorder

The mesocorticolimbic dopamine system (or the so‐called brain reward system, Figure 1) is one of the established neurobiological systems involved during the development and maintenance of alcohol dependence and thus one potential treatment target. Here, we aim to review the animal and human data describing the role of dopamine and the mesolimbic dopamine system during acute and chronic alcohol exposure. Finally, preclinical and clinical studies evaluating the potential of available dopaminergic agents as well as indirect dopamine modulators as novel medications for alcohol dependence are discussed.

Finally, we can pharmacologically probe the contribution of different regulatory systems, including the D2 dopamine autoreceptor and nicotinic acetylcholine receptor (nAChR), to dopamine release. In healthy controls, alcohol consumption stimulates dopamine release mediating its reinforcing effects. Repeated bouts of intoxications will overtime downregulate the dopamine activity in the mesocorticolimbic pathway, leading to an increased risk of developing alcohol dependence and other impulse control disorders. Further, it has been speculated that this dopamine deficiency is responsible for driving craving and compulsive drinking and contributes to relapse even after a period of protracted abstinence 18, 19.

1. Virtually all brain functions depend on a delicate balance between excitatory and inhibitory neurotransmission.
2. Although the study of neural integration is in its infancy, enough has been learned to help guide future research.
3. The study by42 found conflicting results for male and female subjects, with female subjects showing AD only on the basis of alcohol disorder.44 In their study of alcohol-dependence in Polish population reported negative association between Taq1A allele and AD.
4. In addition, aripiprazole has been shown to reverse alcohol‐induced place preference and anxiety‐like behaviour in mice 182.
5. Genetic susceptibility linked to thiamine transporter genes may be involved in the development of WKS in vulnerable patients.

While having a drink from time to time is unlikely to cause health problems, moderate or heavy drinking can impact the brain. In clinical trials in Sweden, alcohol-dependent patients who received an experimental drug called OSU6162, which lowers dopamine levels in rats, experienced significantly reduced alcohol The Effects of Living With an Alcoholic Spouse cravings. Functional connectivity mediation of dopamine depletion effects on (A) attentional bias on the blink task and (B) attentional bias on the reward task. Significant indirect effects indicate the functional connection significantly mediated the effect of beverage type on attentional bias. C is the direct effect without the mediator, and c′ is the effect after entering the mediator.

Dopamine levels fall, and the euphoric buzz goes with it, but your brain is looking to regain the feeling caused by the increased level of dopamine. Eventually, you rely fully on alcohol to generate dopamine release, and without it, you experience withdrawal symptoms. Given the central role of dopamine in alcohol addiction, researchers are exploring potential treatments targeting the dopamine system for alcohol use disorders. Some approaches under investigation include medications that modulate dopamine function, such as dopamine receptor agonists or antagonists.