EnglishOther lines of research related to alcohol withdrawal reinforce this model of alcohol-related changes in DA. Although numerous studies have attempted to clarify dopamine’s role in alcohol reinforcement by manipulating dopaminergic signal transmission, these investigations do not allow any firm conclusions (for a review, see Di Chiara 1995). The comparison of alcohol’s effects with the effects of conventional reinforcers, such as food, however, provides some clues to dopamine’s role in mediating alcohol reinforcement. The alcohol-induced stimulation of dopamine release in the NAc may require the activity of another category of neuromodulators, endogenous opioid peptides.
“I’ve seen cases where I wouldn’t recognize a patient based on how they’re acting.” Brain damage (and symptoms like brain fog) can also be caused by cirrhosis of the liver, another common complication of long-term, heavy drinking. Drinking to avoid feeling bad leads to higher and higher levels of consumption, which can cause greater damage to the brain and the rest of the body. Alcohol kills cells and damages cellular networks in the brain, for example, and it’s not entirely clear to what extent they can grow back. Alcohol also lowers inhibitions and clouds judgment, which could lead a person to engage in risky behaviors like having unprotected sex or driving a car while drunk. And if a person has an underlying mental health disorder, like depression or bipolar disorder, alcohol can exacerbate symptoms and increase mood swings. According to the CDC, binge drinking is defined as consuming four or more alcoholic drinks for women or five or more alcoholic drinks for men on the same occasion.
Abstract
Serotonin’s actions at the synapses normally are tightly regulated by proteins called serotonin transporters, which remove the neurotransmitter from the synaptic cleft after a short period of time by transporting it back into the signal-emitting cell. Consequently, serotonin can affect neighboring neurons only for a short period of time. Any interference with serotonin transporter function extends or diminishes the cells’ exposure to serotonin, thereby disrupting the exquisite timing of nerve signals within the brain. The net result of such disruptions is abnormal brain activity, which can lead to psychological problems or mental illness. One prominent example of a psychological disorder that appears to involve inappropriate serotonin use in the brain is depression (Baldessarini 1996); some of the most effective antidepressant medications act on the serotonin transporters to prolong the neurotransmitter’s activity.
Experiments in mice showed that when given Valium regularly, not only did they develop a tolerance to it, but they also developed an increased tolerance to alcohol. Called cross-tolerance, it indicates that both drugs act at the same receptor, the GABA receptor. Mounting evidence suggested that alcohol acted at GABA receptors, but research had still been unable to pin down a specific mechanism.
Dopamine as a Treatment Target for Alcoholism
Additional studies show a compensatory decrease in adenosine activity following long-term alcohol exposure (Valenzuela and Harris 1997). When the concentrations of different neurotransmitters were determined in various brain regions of these animals, the levels of serotonin and its metabolites were lower in P rat brains than in NP rat brains. The differences were particularly pronounced in the nucleus accumbens, a brain area thought to be involved in the rewarding effects of ethanol (LeMarquand et al. 1994b; McBride et al. 1995). Moreover, the P rats had fewer serotonergic neurons in the raphe nucleus compared with the NP rats (Zhou et al. 1994), a finding that could explain the reduced serotonin and serotonin-metabolite levels. The observation that P rats naturally have low serotonin levels supports the hypothesis that heavy drinking may partly represent an attempt to normalize serotonin levels in certain key brain regions, because acute alcohol consumption can elevate serotonin levels. Recent studies also have evaluated the numbers and properties of different serotonin receptors in P and NP rats.
These observations have stimulated many studies on dopamine’s role in alcohol abuse and dependence, also with the intent of finding new pharmacological approaches to alcoholism treatment. This review summarizes some of the characteristics of dopaminergic signal transmission as well as dopamine’s potential role in alcohol reinforcement. Countless human and rodent studies have explored the relationship between the dopaminergic signaling and alcohol abuse with evidence amassed from anatomical, physiological, pharmacologic, genetic, and behavioral research. The second line of evidence implicating serotonin in the development of alcohol abuse stems from studies of compounds that interfere with the functions of the transporters that remove serotonin from the synapse.
Alcohol and your mood: the highs and lows of drinking
It’s not clear if alcohol directly acts on all those receptors or if they’re a downstream result of its action elsewhere. Classification of drugs can be explained by their chemical targets within the brain. Depressants target a chemical called GABA, the primary inhibitory neurotransmitter within the brain. Alcohol has been described as a ‘favourite coping mechanism’ in the UK and is commonly used to try and manage stress and anxiety, particularly in social situations, giving us what’s sometimes called ‘Dutch courage’ [2]. Since alcohol can increase the body’s production of dopamine and serotonin, two of the body’s ‘happy hormones’, it can temporarily make us feel less anxious.
Long-term alcohol exposure results, however, in a compensatory increase in calcium flow, which becomes excessive when alcohol consumption ceases. Evidence suggests that medications that inhibit calcium channel function (i.e., calcium channel blockers such as nimodipine) can relieve the seizures accompanying alcohol withdrawal (Valenzuela and Harris 1997). Indeed, in rodent models, alcohol abstinence or withdrawal periods are often followed by enhanced rebound alcohol drinking, the alcohol deprivation effect [66]. This alcohol deprivation effect has also been observed in cynomolgus macaques [8]. Accordingly, the macaques in Cohort 3 underwent three, 1-month long abstinent periods during the experiment. 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.
A dedicated hypothalamic oxytocin circuit controls aversive social learning
A subsequent group of researchers found that drinking increases levels of norepinephrine, the neurotransmitter responsible for arousal, which would account for heightened excitement when someone begins drinking. Norepinephrine is the chemical target of many stimulants, suggesting that alcohol is more than merely a depressant. Elevated levels of does alcohol affect dopamine norepinephrine increase impulsivity, which helps explain why we lose our inhibitions drinking. Drunken brains are primed to seek pleasure without considering the consequences; no wonder so many hook-ups happen after happy hour. At the same time, behavioral researchers sought to understand the physiological and psychological effects of drinking.