Neuroscience: The Brain in Addiction and Recovery National Institute on Alcohol Abuse and Alcoholism NIAAA

“Intoxication occurs when alcohol intake exceeds your body’s ability to metabolize alcohol and break it down,” explains Amanda Donald, MD, a specialist in addiction medicine at Northwestern Medicine. Adolescent brains are more vulnerable to the negative effects of alcohol than adult brains. Misuse of alcohol during adolescence can alter brain development, potentially resulting in long-lasting changes in brain structure and function. Alcohol interferes with the brain’s communication pathways and can affect the way the brain looks and works. Alcohol makes it harder for the brain areas controlling balance, memory, speech, and judgment to do their jobs, resulting in a higher likelihood of injuries and other negative outcomes. Long-term heavy drinking causes alterations in the neurons, such as reductions in their size.

Dopamine and AUD

These changes are particularly pronounced following repeated exposure to alcohol and were proposed to regulate sensitization [38]. Alcohol reduces glutamate excitotoxicity (VTA); enhances GABA inhibitory activity (VTA) and enhances dopamine release from the VTA to NA by disinhibiting GABA via endogenous opioids. The dysfunction of these systems is responsible for acute alcohol intoxication, alcohol dependence, and withdrawal syndrome. Different alleles of the genes in the various pathways are being studied in different population groups across the world.

MECHANISMS OF ALCOHOL RELATED BRAIN INVOLVEMENT

At experimenter-selected doses they elevate dopamine levels [158–161] and it has been suggested that they are addictive for this reason [24]. The developing adolescent brain is particularly vulnerable to alcohol-related harm. Alcohol is a powerful reinforcer in adolescents because the brain’s reward system is fully developed while the executive function system is not, and because there is a powerful social aspect to adolescent drinking. Specifically, prefrontal regions involved in executive functions and their connections to other brain regions are not fully developed in adolescents, which may make it harder for them to regulate the motivation to drink. Because the brain is adaptable and learns quickly during adolescence, and because alcohol is such a strong reinforcer for adolescents, alcohol use is more likely to be repeated, become a habit, and eventually evolve into a problematic drinking pattern that may lead to AUD.

Dopamine depletion effects on VTA FC

• This approach can also be tremendously useful for determining pre- versus post-synaptic localization of different receptors.
• The reward-predicting stimuli that lead an animal to anticipate rewards—both natural rewards and drug rewards—are established by this kind of learning [3, 25].
• However, D1 receptors activate Gs proteins thereby increasing cAMP, whereas D2 receptors activate Gi proteins thereby decreasing cAMP.
• Similarly, we did not see any significant changes in mRNA levels of the nAChR subunits.
• A better understanding of how alcohol affects these diverse and interlinked mechanisms may lead to the identification of novel therapeutic targets and to the development of much-needed novel and efficacious treatment options.
• The kappa-opioid receptor (KOR) and its endogenous ligand dynorphin peptide have been an area of great interest.

So why is it so hard to know whether alcohol is good or bad for us—especially for our brains? In this post, we’ll explore the current science and some practical ideas on how to approach the topic. Maintaining the bridge between translational insights across species and taking advantage of each animal models’ unique tools and systems will bring the field closer to achieving a comprehensive understanding of AUD and facilitate effective treatment strategies. Voltage-gated calcium channels (VGCCs) are voltage sensitive ion channels embedded in the membrane of excitable cells that regulate the rapid entry of Ca2+ during depolarization. At the core of these channels is a principal pore-forming α1 subunit and up to 3 supporting α2δ, β, and γ subunits. There are 5 classified types of high-voltage-activated channels (L-type, P/Q-type, N-type, R-type, and T-type) and 3 low-voltage-activated channels each composed of a sole α1 subunit (Figure 1e; Table 1).

Dopamine depletion procedure

The results point to a significant role of dopamine for both alcohol and non-drug reward AB and indicate that specific dopamine-dependent functional connections between frontal, limbic, striatal, and brainstem regions mediate these behaviors. Epigenetic pathways are tightly interlinked, resulting in increased complexity of alcohol-induced epigenetic dysregulation. For example, chronic exposure to alcohol led to long-lasting reduction of H3K27ac and parallel induction of H3K27me3 at the immediate early gene Arc in the CeA of rats [22]. These acetylation/methylation changes resulted in decreased expression of the non-coding Arc eRNA (enhancer RNA; short non-coding RNAs transcribed from enhancers) and affected Arc transcription [22]. These findings emphasize that alcohol does not affect specific epigenetic mechanisms in a vacuum, and the potential interaction of these regulatory pathways is critical to consider. Alcohol is the first thing people go for when they are at a social gathering and are looking to have a pleasant time.

Publication types

Here, we outline a framework for understanding alcohol-induced changes in the brain, which can help you appreciate the challenges faced by many patients with AUD when they try to cut back or quit drinking. We then describe evidence-based treatments you can recommend to patients to help the brain, and the patient as a whole, to recover. Those feelings are often referred to as a “high,” which people are known to “chase.” The role that dopamine plays in the brain’s reward system is what links it to addiction. While dopamine addiction isn’t really possible, you can get hooked on doing things that make you feel that rush of pleasure. Dopamine is a neurotransmitter—or brain chemical—that people sometimes call the “feel good” hormone. That’s because when we do things that trigger the release of dopamine, we feel good.

Behavioral and neurobiological consequences of altered dopamine signaling

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. Faster dopamine uptake in the female subjects would have the net effect of decreasing the duration of neuromodulation produced by this transmitter. However, the increased uptake rate could be countered by the observed enhanced release, at least in female caudate. Nonetheless, altered dopamine kinetics or release could affect dopamine-dependent synaptic plasticity [42] that might subsequently affect new learning and behavioral flexibility. Indeed, in the multiple abstinence cohort, in which alcohol treated subjects had significantly less dopamine release, a separate study found that alcohol-consuming subjects had poorer cognitive flexibility relative to controls [43, 44].

Aging with alcohol-related brain damage: Critical brain circuits associated with cognitive dysfunction

The Carolina Alcohol Use Patterns Questionnaire (CAUPQ [61]) was used to estimate a total number of adolescent (0–21 years) binge episodes (see Supplementary Materials) and quarter-root transformed before statistical analysis. Recently, a previously unanticipated mechanism was identified linking alcohol metabolism to alcohol-induced epigenetic impairments by way of direct incorporation of alcohol-derived acetate into brain histone acetylation [24]. This was driven by the nuclear translocation of metabolic enzyme acetyl-CoA synthetase 2 (Acss2), inhibition of which prevented alcohol-induced changes of histone acetylation and gene expression, and blocked conditioned place preference to alcohol [24]. This and related epigenetic-metabolic pathways [25] represent a radically novel mechanism of alcohol-induced transcriptional changes.

Associated Data

Here, we provide an update on alcohol research, focusing on multiple levels of alcohol-induced adaptations, from intracellular ones to changes in neural circuits. A better understanding of how alcohol affects these diverse and interlinked mechanisms may lead to the identification of novel therapeutic targets and to the development of much-needed novel, efficacious treatment options. Uncontrolled or abusive alcohol consumption is an undisputed global health concern with significant social costs and economic burdens.1 Individuals suffering from Alcohol Use Disorder https://ecosoberhouse.com/ (AUD) often display persistent patterns of alcohol use that escalates from abuse to dependence. Underlying these maladaptive behaviors are short and long-term changes to neurotransmitters, receptors, synapses, and circuits. Understanding the neuromolecular targets of alcohol and how they are altered is critical to the development of novel AUD treatment strategies. Alcohol-induced epigenetic alterations are often mediated by altered expression or activity of epigenetic enzymes, which thus represent a promising new avenue for targeted therapeutic interventions.

Potassium Channels

• For instance, manipulations of striatal dopamine D2 receptors (D2Rs), adenosine 2A receptors, or activity of fast-spiking interneurons, among others, alter excessive drinking behaviors [104–106].
• When compared alongside the male macaques from Cohort 2, which did not undergo multiple abstinence periods, we can begin to assess the effect of the abstinence periods on our measured outcomes, as well as, the persistence of these outcomes.
• In a conditioned place preference study, alcohol is reported to be dopamine-dependent in alcohol-naive animals but not in withdrawn, experienced, animals [132].
• We also found that dopamine D2/3 autoreceptor function was reduced in male, but not female, alcohol drinkers relative to control groups.
• Lastly, new tools, like the fly TransTimer,144 are providing a means in which to study the real-time spatiotemporal dynamics of gene expression.

However, what remains to be seen is a definitive consensus on a causative allele of alcoholism. There are conflicting reports in this regard with different population groups having different alleles as risk factors. Moreover, new alleles are also being discovered wherein an association exists between the stated allele and alcoholism. As a reviewer, I would alcohol and dopamine suggest one possible way to overcome much of the conflicting reports would be to perform studies with a much larger sample size. Such efforts are hampered by inadequate funding, so collaborative efforts on a national scale, combining the skills and infrastructures of different hospitals and psychiatric care centers could potentially overcome this problem.

Categorised in: Sober living

This post was written by vladeta