How does alcohol influence the mind? A look into the brain and its genes.

* Scientific study references are indicated in (). These can be found at the bottom of the article, and can be clicked on to access the original reports.

The holiday season is over, and in the words of Sean Connery, the damage is done. But aside from the myriad ways in which alcohol harms brain function, what most of us perhaps find more interesting is the question of alcohol’s effect on subjective experience. What events does alcohol consumption produce in the brain that might explain why this substance makes us feel the way it does – relaxed, numb to the senses, and uncoordinated? And where does the risk of becoming hooked come from?

Why does alcohol sedate, numb and make us uncoordinated?

The relaxing effect of alcohol is primarily underpinned by the fact that ethanol molecules interact with a class of so-called GABAA receptors – proteins which are embedded in the membranes of brain cells, or neurons (11). Most often, these receptors are activated by the brain’s own neurochemical GABA (short for Gamma Amino-Butyric Acid), which inhibits the ability of neurons to become excited by signals being sent by other cells. As a result, affected neurons become unlikely to accept other neurons’ attempts to communicate, and thus temporarily become ‘deaf’ to incoming information.

The power to suppress other neurons makes GABA-releasing cells fundamentally important in the workings of the brain. Since they are capable of precisely timing when other neurons can and cannot receive signals from various regions of the brain, many neuroscientists consider these cells the architects of neuronal communication (14). So it’s probably unsurprising that substances which influence GABAA receptors interfere with the brain and, by extension, our subjective experience. This is where alcohol comes in.

Experiments have revealed that alcohol strongly enhances the suppressive effect of certain GABAA receptors (1, 3, 11, 16). This occurs because ethanol molecules are able to attach themselves to specific pockets in the receptor, which subtly changes its shape and allows GABA molecules to fit more snugly into the receptor when they are released from communicating cells.


This means that, as ethanol floats around and interacts with a neuron’s GABAA receptors, it both enhances the probability that these receptors will become activated and increases the period of time over which they will remain active (32). Ultimately, this produces more powerful suppression of the affected neuron.

The image below comes from an experiment in which researchers recorded from the membranes of mouse neurons while applying droplets of GABA combined with various doses of ethanol (1).


It’s clear that stimulating GABA receptors with the natural neurochemical has a negative influence on this neuron’s level of excitability (making it less likely to produce a signal). But quite importantly, we can see that this suppressive effect is boosted by alcohol, more so with increasing concentrations. While alcohol can’t activate GABAA receptors alone, we have solid evidence that it acts in concert with the brain’s own neurochemical to silence neurons more strongly than natural conditions permit. This effect was found in 70% of the studied neurons (1). Indeed, GABAA receptors are some of the most common receptors in the mammalian nervous system, which means that the suppressive effect of alcohol is bound to be quite a common phenomenon.

Now let’s imagine that this occurs all over the brain as we have a drink. Brain regions which normally receive information from the skin about harmful events (eg. dangerous temperatures or cuts) would become slightly less receptive to such signals, which likely numbs our perception of pain (17). Neurons that normally receive constant updates from the retina, ears, tongue, and skin would also become more silent, as signals travelling from these senses become somewhat subdued by the indifference of the many cells which are under the suppressive influence of GABAA receptors modified by ethanol. The senses become a bit blunted and less reliable, as perhaps evidenced by the ‘alcohol jacket’, which the Urban Dictionary elegantly defines as ‘a non-tangible source of warmth, deriving from the mass consumption of alcohol’. Indeed, the brain generally becomes a quieter place under the influence of ethanol. The PET scan below shows how the consumption of glucose (the brain’s energy source) goes downhill as we enter a state of intoxication.Pic3The effects of alcohol are especially potent in the cerebellum – a region at the back of the brain which is particularly enriched in the GABAA receptor types that are maximally sensitive to ethanol (18).

Pic4We know that the cerebellum is critical for coordinating movements. Damage to this region makes individuals less able to control their eye movements, produce the complex tongue and lip movement sequences required for speech, regulate their posture, and correctly estimate the distance their limbs need to travel to reach objects (29). This is why cerebellar patients may have slurred speech, a strange manner of walking, and a tendency to slightly miss items they aim to grab with their hands. If any of these symptoms sound familiar to you, it’s because they also emerge when communication between neurons in the cerebellum becomes muffled when alcohol reaches the brain (10). This is why asking individuals to walk in a straight line or touch their nose is commonly used as a quick test of intoxication.

Even rats experience disorientation at the hands of ethanol meddling with cerebellar GABAA receptors. Interestingly, researchers have found that rats with an extremely low tolerance for alcohol have genetic mutations (DNA changes) which increase the sensitivity of GABAA receptors of the cerebellum to the modifying effects of alcohol (25). Essentially, these rats’ brains undergo more widespread and potent inhibition during alcohol consumption, causing a more dramatic deterioration of motor skills. Such mutations likely also affect how humans handle their drinks.

The key to understanding why alcohol also slows our reflexes lies with the spinal cord. This part of the nervous system generates most of our reflexes, from rapid withdrawal of the hand when we touch something hot or sharp, to the classic knee jerk reflex. When it comes to the effects of alcohol on reflexes, the culprits are receptors which are activated by glycine – the dominant inhibiting neurochemical of our spinal cord. We know that glycine receptors are essential for regulating the intensity of our reflexes, as individuals with genetic mutations which disturb these receptors tend to have highly exaggerated reflexes (12). We also know that the suppressive effect of glycine receptors is boosted by the presence of ethanol similarly to how this occurs with GABAA receptors (2, 9, 13). Now let’s picture an intoxicated person encountering a situation that triggers a reflex. The spinal cord instantly attempts to adjust how strongly this person’s muscles will react by releasing glycine, which gently constrains the muscles by stimulating the glycine receptors on neurons which connect to them. However, the boost that ethanol gives to these suppressive glycine receptors means that the muscles become silenced all too intensely and the reflex is ultimately subdued (35).

Perhaps more interesting is the fact that glycine receptors are also found in the brain (4, 24), where alcohol causes them to produce some important psychological effects. In part, this occurs because glycine interferes with the dopamine neurochemical system, which might shed some light on why people can become hooked on alcohol. Importantly, it might also hold the key to future drug treatments for alcohol addiction.

Why do we crave alcohol? A story of dopamine and genes.

We know that dopamine is critical for inducing addiction and the desperation that comes with it to get a hold of more rewarding substance. When rats are given an opportunity to press a lever resulting in direct injections of cocaine into their own brains, they go on binges during which they press compulsively until they are exhausted. Such injections are known to immediately increase dopamine levels in the nucleus accumbens (NA) – a deep-brain cluster of cells which is a critical component of the brain’s reward system (30).Pic5.pngThat dopamine provokes cravings is widely accepted. It compels individuals to seek the thing which provided that dopamine spike in the first place, often regardless of whether they actually enjoy the thing they crave (7). Researchers have known for a while that ethanol consumption increases dopamine levels in the nucleus accumbens (819). Dopamine appears to be quite important here, since preventing this neurochemical from influencing neurons, by blocking dopamine receptors, makes rats less likely to choose to drink more alcohol (27). Over a decade ago, researchers found that this dopamine rush appears to be largely underpinned by the effects of alcohol on the glycine receptors which are clustered around neurons in the brain’s reward centres (24).

This was discovered when researchers observed that the massive dopamine release that occurred when rats were given alcohol was prevented by a drug which blocked glycine receptors. On the other hand, dripping glycine directly into the brain (which naturally stimulated these receptors) boosted the intoxicated dopamine burst. The fact that activating glycine receptors in the nucleus accumbens excited dopamine release seems a bit of a mystery, given what we know about glycine’s inhibiting effect on neurons. To understand roughly how researchers attempted to explain this somewhat surprising finding, let’s look inside the connections between neurons in the brain’s reward centres:


Glycine is by no means the only neurochemical system known to stimulate dopamine release when we are intoxicated (21, 22, 36). However, it’s increasingly considered to be a key to understanding how alcohol influences the brain both moments after we have a drink and in the long term. Indeed, repeated consumption of alcohol pushes the brain to adjust, and researchers have so far found that this involves altering the activity of an astounding 168 genes involved in several neurochemical systems, including glycine (33).

Repeated dopamine bursts produced during chronic alcohol intake also suppress the activity of a particular gene producing the critical dopamine receptor, D2 (26). This receptor is found in the endings of dopamine-releasing cells, where it keeps a lid on neurochemical release to prevent build-up. The fact that repeated alcohol exposure reduces production of this receptor means that over time, drinking might interfere with the brain’s normal brakes on dopamine release. In rats, disrupting the workings of D2 receptors is known to speed up the development of addiction to substances ranging from cocaine to food (6). All of this points to a somewhat worrying reality – in consuming alcohol, people might be making their brains increasingly sensitive to the experience of reward that comes with substances like alcohol, drugs and food, which gradually makes people more desperate to seek them out.

The importance of glycine receptors in this addictive chain of events has given rise to a new generation of potential drug treatments for alcoholism. Researchers recently found that treating alcohol-addicted rats with a drug that blocks glycine receptors reduced their preference for booze over water, as well as prevented drinking binges which tend to occur after a period of alcohol deprivation (20). Similar drugs have been found to reverse the worrying changes in activity of about a third of the genes known to be affected by chronic drinking (33). In the next few years, more research will reveal how we can harness our knowledge of the glycine system to tackle the problematic effects of alcohol.



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10 thoughts on “How does alcohol influence the mind? A look into the brain and its genes.

  1. This was a fascinating read. Thank you for the work you put into it!

    I would love to see more articles like this on the influence and mechanisms of other common drugs.


  2. That was really interesting. I’ve been trying to put together an infograph on alcohols affects on the body and this answered a lot of ‘whys’.


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