Alcohol Addiction - How does it happen?
Alcohol, by far, is one of the most commonly used psychoactive substances consumed. Continuous long term consumption of alcohol over time can lead to the development of tolerance and withdrawal. This is due to the fact that alcohol affects the mesolimbic dopamine system (Tomkins, 2001). Similar to other drugs, alcohol increases the release of dopamine, which is a neurotransmitter that induces feelings of pleasure and reward. As a result, the activation of the reward system is a common factor in repeated consumption of alcohol.
In normal neurotransmission, the neurotransmitter, GABA, gets released from the presynaptic neuron and into the synaptic cleft. GABA binds to a receptor that is unique to the GABA molecule and the ion channel on the postsynaptic neuron opens, letting ions (chloride ions in particular) flow into the neuron. This signals the depolarization of the neuron and propagates the affect of GABA. Eventually, GABA will detach from the receptor and get taken back up into the pre-synaptic neuron. However, when alcohol enters the bloodstream, it binds directly to the receptor and keeps the ion channel open longer, prolonging the inhibitory affects of GABA. The chloride ions that flow into the neuron make the post-synaptic neuron potential more negative, making it harder to excite the neuron. Essentially, the brain becomes sedated from the affects of GABA which leads to latent reaction times, relaxed breathing, decrease in mental cognition, and numbing of pain. Alcohol affects more than just the GABA receptors; it can also bind to the receptors for acetylcholine and the NMDA receptors for glutamate (CRI, 2012). As a result, alcohol also reduces the excitatory effects of glutamate. Research also shows that alcohol helps increase the release of dopamine by inhibiting the enzymes that typically break down dopamine.
Over time, the human body is able to adapt and function normally at higher levels of GABA. Moreover, the adaptation makes the NMDA receptors more sensitive to glutamate while desensitizing the GABAergic receptor. Once this occurs and the person suddenly stops drinking, he or she may begin to experience withdrawal symptoms, like anxiety, insomnia, jitters, emotional discomfort, and possibly tremors. Sometimes, even after long times without alcohol, brain abnormalities can still exist and cause discomforts and cravings.
But, you know, not everyone who drinks gets addicted. So, what's up with that?
Studies in human genetics reveal correlations between alcoholism and dopamine D2 receptors and dopamine transporters (Cowen, 1999). In the brain of alcoholics, both the D2 receptor and dopamine transporter densities are higher than in non-alcoholics (Repo, 1999., Volkow, 1996, Tupala, 2000.). This finding implicates that the increased density of these dopamine receptors make a person more vulnerable to addiction or may cause relapse in alcohol-dependent patients. This reason would explain why some people are more susceptible to addiction to alcohol than others. Since the density of the D2 receptor and dopamine transporter is determined by nerve cell development and ultimately genes, alcoholism could be genetically related. However, the exact mechanism that leads to addiction is difficult to identify (Tomberg, 2010). While the exact mechanism of addiction has yet to be discovered, the impact it has on the brain is not a mystery.
In normal neurotransmission, the neurotransmitter, GABA, gets released from the presynaptic neuron and into the synaptic cleft. GABA binds to a receptor that is unique to the GABA molecule and the ion channel on the postsynaptic neuron opens, letting ions (chloride ions in particular) flow into the neuron. This signals the depolarization of the neuron and propagates the affect of GABA. Eventually, GABA will detach from the receptor and get taken back up into the pre-synaptic neuron. However, when alcohol enters the bloodstream, it binds directly to the receptor and keeps the ion channel open longer, prolonging the inhibitory affects of GABA. The chloride ions that flow into the neuron make the post-synaptic neuron potential more negative, making it harder to excite the neuron. Essentially, the brain becomes sedated from the affects of GABA which leads to latent reaction times, relaxed breathing, decrease in mental cognition, and numbing of pain. Alcohol affects more than just the GABA receptors; it can also bind to the receptors for acetylcholine and the NMDA receptors for glutamate (CRI, 2012). As a result, alcohol also reduces the excitatory effects of glutamate. Research also shows that alcohol helps increase the release of dopamine by inhibiting the enzymes that typically break down dopamine.
Over time, the human body is able to adapt and function normally at higher levels of GABA. Moreover, the adaptation makes the NMDA receptors more sensitive to glutamate while desensitizing the GABAergic receptor. Once this occurs and the person suddenly stops drinking, he or she may begin to experience withdrawal symptoms, like anxiety, insomnia, jitters, emotional discomfort, and possibly tremors. Sometimes, even after long times without alcohol, brain abnormalities can still exist and cause discomforts and cravings.
But, you know, not everyone who drinks gets addicted. So, what's up with that?
Studies in human genetics reveal correlations between alcoholism and dopamine D2 receptors and dopamine transporters (Cowen, 1999). In the brain of alcoholics, both the D2 receptor and dopamine transporter densities are higher than in non-alcoholics (Repo, 1999., Volkow, 1996, Tupala, 2000.). This finding implicates that the increased density of these dopamine receptors make a person more vulnerable to addiction or may cause relapse in alcohol-dependent patients. This reason would explain why some people are more susceptible to addiction to alcohol than others. Since the density of the D2 receptor and dopamine transporter is determined by nerve cell development and ultimately genes, alcoholism could be genetically related. However, the exact mechanism that leads to addiction is difficult to identify (Tomberg, 2010). While the exact mechanism of addiction has yet to be discovered, the impact it has on the brain is not a mystery.
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Alcohol's Effect on Neurotransmitters and their receptors:
Neurotransmitter | Function | Resulting Effect |
---|---|---|
Glutamate | Inhibits glutamate receptor function | muscular relaxation, discoordination, slurred speech, staggering |
GABA (gamma-aminobutyric acid) | enhances GABA receptor function and allow the inflow of negative ions | feelings of calm, anxiety-reduction, and sleep |
Dopamine | Raise dopamine levels | Feelings of excitement and stimulation |
Endorphins | Raise endorphin levels | endorphin high and reduction of feeling of pain |
Alcohol & The Brain
Research studies converge on the theory that an alcoholic without structural brain changes shows cognitive impairment (Akine et al., 2007). Consumption of alcohol causes changes in the behavior of a person, such as increased euphoria and lessened social inhibitions. While the mechanism of alcohol addiction is not certain, the dopamine system, which is involved with the rewarding affects of psychoactive drugs, including alcohol, may be an important factor in alcohol addiction. The ventral tegmental area (VTA) of the brain and the nucleus accumbens (NAcc), which are connected by the medial forebrain bundle (MFB) are especially important in producing the rewarding effects of alcohol. These areas innervate other areas of the brain such as the prefrontal cortex and the frontal cortex (both of which are responsible for planning and judgment) and the amygdala, which is responsible for emotions and conditioned effects. All of these areas are involved in the reward system of the brain. These behavioral changes are caused by ethanol binding to different channels within the brain and affecting neurotransmission. Several different systems are affected by alcohol, which are elaborated upon below. The mesolimbic dopamine system is the main reward system in the brain. Many other pathways involving different neurotransmitters are also connected to the dopamine system and thus also affect the reward system. The reward system that is initiated by alcohol consumption is thought by some to be what ultimately causes addiction. Addiction involves functions of the areas of the brain previously mentioned. Many neurotransmitter systems are involved in what causes alcohol to be addicting, such as the glutamatergic, GABAergic, and the opioid systems. Alcohol affects the activity of the receptors in these systems which can change the activity of the mesolimbic dopamine activity.
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CT and MRI scans of chronic alcoholics show: reduced gray and white matter volumes, losses in the frontal lobes as well as in medial temporal and parietal cortices, in subcortical structures (thalamus, caudate nucleus), in the cerebellar cortex , and in the cerebellar vermis, thinning of the corpus callosum (see the section on alcohol and motor control), reduced volume in the pons, and reduction in hippocampal volume (Tomberg, 2010). Chronic alcoholics show impaired reaction times and reduced verbal frequency. The images below show the differences in the brain from non-alcoholics and alcoholics.
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Mesolimbic dopaminergic system
As mentioned above, the mesolimbic dopaminergic system is vital for transmitting the rewarding affects of alcohol. Each of the systems below is interconnected with the mesolimbic dopaminergic system. It originates in dopaminergic neurons (hence its name) in the VTA. When alcohol is consumed, it causes an increased release of dopamine from the NAcc which increases the extracellular concentration of dopamine. This is most likely due to the increased firing rate of the neurons causing the release of the dopamine. Reinforcement of alcohol is thought to be directly related to the increased firing rate. The rate of the increase in the amount of dopamine in the NAcc and in the striatum is highly related to the reinforcement of alcohol.
If alcohol is consumed regularly, the communication between synapses in the mesolimbic dopaminergic system is changed. The function of dopamine is decreased in people who have been drinking for a long period of time, and is involved in the change in behavior of the person. One aspect influencing alcohol dependence is thought to be the DRD2 TaqI A polymorphism. (Tomberg, 2010)
If alcohol is consumed regularly, the communication between synapses in the mesolimbic dopaminergic system is changed. The function of dopamine is decreased in people who have been drinking for a long period of time, and is involved in the change in behavior of the person. One aspect influencing alcohol dependence is thought to be the DRD2 TaqI A polymorphism. (Tomberg, 2010)
Gabaergic System
The modification of GABA receptors by alcohol is one of the ways the reward system is reinforced. The GABA interneuron can reduce the amount of dopamine released.
When alcohol is consumed repeatedly, the person's tolerance for alcohol increases. This is thought to be related to the downregulation of the GABAergic system. The function of the GABAergic system is also reduced by changing the amount of GABAA-R subunits. The GABAA-Rs outside of the synapses are activated at lower alcohol concentrations, than the GABAA-Rs inside the synapses which could increase alcohol tolerance (Tomberg, 2010).
When alcohol is consumed repeatedly, the person's tolerance for alcohol increases. This is thought to be related to the downregulation of the GABAergic system. The function of the GABAergic system is also reduced by changing the amount of GABAA-R subunits. The GABAA-Rs outside of the synapses are activated at lower alcohol concentrations, than the GABAA-Rs inside the synapses which could increase alcohol tolerance (Tomberg, 2010).
Glutamaergic System
The glutamergic system involves the neurotransmitter glutamate which is thought to be regulated modifying characteristics of dopamine. When a large amount of alcohol is consumed, it reduces the excitatory input to the glutamergic system. It also blocks certain NMDA receptors in the brain. The dopamine signal and the signal from the glutamate receptors meet in the nucleus accumbens. Alcohol increases the amount of interaction between dopamine and the NMDA receptors. This interaction helps reinforce ethanol and possibly increases the degree of addiction. If enough alcohol is consumed repeatedly, the NMDA receptors are blocked chronically. This increases the alcohol tolerance of the person and leads to a dependence on alcohol. The dependence of the person on alcohol is thought to be related to the tolerance of the NMDA receptor antagonists and to the increased regulation of the NMDA receptors. (Tomberg, 2010)
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