Alcohol Addiction and Neurotransmitters

Originally used for a research article, but I thought it was interesting.

Alcohol is one of the worlds most used drugs. In cases of addiction, there is more at play than simply habitual routines. Often these (addictive substances) are used chronically as they actively change our brain chemistry. Looking more specifically at alcohol addiction, alcohol modulates the brain reward system that is important in initiating and maintaining behavioural patterns (Tomkins & Sellers, 2001).

The medial forebrain bundle (MFB) (connecting the ventral tegmental area to the nucleus accumbens (NAcc)), innervates the amygdala [emotions] and cortical areas [senses]. These areas are responsible for emotional expression, reactions to cues, planning and judgement (Tomkins & Sellers, 2001). Basically, these areas are responsible for assessing motivations, and turning those into actions. In the MFB, neurons respond to dopamine, noradrenaline and serotonin. These are important neurotransmitters connected to feeling good, while noradrenaline helps control blood pressure and heart rate. Serotonin is largely thought of in relation to joy. However, the dopaminergic pathways are mostly associated with the reward connection, pleasure.

Issues with dopamine receptors and transporters may increase the likelihood of alcohol abuse. Rewards increase dopamine within the NAcc, but other neurotransmitters do play a role in alcohol addiction, such as GABA [relaxing neurotransmitter], serotonin, glutamate - excitatory neurotransmitters (Tomkins & Sellers, 2001; Banerjee, 2014). There are limited allopathic drugs for alcohol addiction directly, though receptor antagonists may be a consideration - antagonising [blocking] dopamine rather than destroying receptors has shown some improvement in rats (Tomkins & Sellers, 2001; Banerjee, 2014).

Short term, alcohol consumption increases dopamine release, even the thought of it, which strongly connects the emotional response to the actions in order to acheive that state again. There are other neurotransmitters that contribute to this process, however dopamine was highlighted due to it's involvement in [all] addictive habits.

Hyperexcitability in the NMDA system [mediating learning and memory] occurred following long-term alcohol use, so perhaps neurotransmitters which bind to these receptors, such as GABA or glutamate are a more useful focus to decrease consumption (Tomkins & Sellers, 2001). However, glutamate levels decrease with alcohol consumption, the receptors they bind to (NMDA receptors) are important in alcohol addiction as they relate to neuroplasticity and the neuron reorganisation that happens when an addiction forms (Banerjee, 2014). I.e. because lots of glutamate is used when we form new habits/ new ways of thinking, it is less freely available. GABA and glutamate balance appear important here. Vengeliene, Bilbao, Molander & Spanagel (2008) reports “glutamate receptors appear to adapt to the inhibitory effects of alcohol by increasing their excitatory activity”, hence the hyperexcitability mentioned previously in chronic cases. More specifically, hyperexcitability when sober or in withdrawal - increasing the craving feeling (Vengeliene, et al. 2008). Hyperexcitability of receptors may increase feelings of anxiety, restlesness, and feel pain more intensely. Glutamate receptors becoming more easily activated can result in the degeneration of dendrites and cell death (Mattson, 2019). Disruptions of glutamate uptake from the synapse have been linked to reduced sensitivity to reward, a symptom of depression (National Academies Press (US); 2011). This ends up with loss of brain tissue in the front cortex, which leads to poorer decision making. With the reduced sensitivity to reward behaviour, things feel very bland, this could cause an increase in consumption in order to chase that original reward feeling (dopamine). Genetic alleles also increase propensity for alcoholism, therefore such efforts will need to be increased (Banerjee, 2014). Creating a balance between GABA and glutamine, by treating with NAC for example, to correct the glutamate dysregulation, may be effective in reversing the neurochemistry changes.

To summarise: several important neurotransmitters are involved in alcohol addiction and it cannot be treated through focussing on one; neither on the volume or sensitivity to one. There are chemical changes to the brain’s responses and sensitivity which increase dependence on alcohol, and further worsen the problem. While focussing on dopamine and glutamate helps us understand the disease process, ultimately, they will affect their opposing neurotransmitters too.

With aggressive and drug dependent treatment of alcoholism, the idea is to avoid creating compensatory changes to other neurotransmitters. Therefore, we need to heal the dysfunctional neurotransmitters/receptors, encourage excitatory responses for other events and provide necessary nutrients to help cope with detoxification and withdrawal (excitability of some receptors, and lack in others). 

References:

Banerjee, N. (2014). Neurotransmitters in alcoholism: A review of neurobiological and genetic studies. Indian Journal of Human Genetics, vol 20. Issue 1. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065474/

National Academies Press (US), (2011). Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary. Institute of Medicine (US) Forum on Neuroscience and Nervous System Disorders. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK62187/

Mattson, M. (2019). Stress: Physiology, Biochemistry, and Pathology. Handbook of Stress Series, vol 3. Chapter 11. Retrieved from: https://www.sciencedirect.com/science/article/pii/B9780128131466000114

Tom, D. & Sellers, E. (2001). Addiction and the brain: the role of neurotransmitters in the cause and treatment of drug dependence. CMAJ, vol 164. Issue 6. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC80880/

Tomko, R., Jones, J., Gilmore, A., Brady, K., Back, S., & Gray, K. (2018). N-acetylcysteine: A potential treatment for substance use disorders. Current Opinion in Psychiatry, vol 17. Issue 6. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993450/

Vengeliene, V., Bilbao, A., Molander, A. & Spanagel, R. (2008). Neuropharmacology of alcohol addiction. British Journal of Pharmacology, vol 154. Issue 2. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442440/