In a study published in the journal Nature Communications, researchers at Wake Forest Baptist Medical Center found that ethanol followed the same biochemical pathway as rapidly effective antidepressants. Consequently, patients with major depressive disorder who ingested ethanol felt non-depressant effects that lasted at least 24 hours. This study supports the high comorbidity between alcoholism and depression and supports the notion of self-medication, although researchers emphasized that alcohol is not a treatment for depression.
“Because of the high comorbidity between major depressive disorder and alcoholism there is the widely recognized self-medication hypothesis, suggesting that depressed individuals may turn to drinking to treat their depression,” said Kimberly Raab-Graham, an associate professor at Wake Forest School of Medicine, in a news realease.
On a molecular level, ethanol is known to block N-methyl-D-aspartate receptors (NMDARs), or proteins associated with learning and memory. It also works with the autism-related fragile X mental retardation protein (FMRP) to induce gamma-Aminobutyric acid (GABA), which stimulates neural activity.
By binding allosterically to NMDARs, ethanol prevents channels associated with these receptors from opening completely. As a result, fewer sodium ions flow into cells, causing less depolarization and less initiation of action potentials. Ethanol also inhibits depolarization by binding allosterically to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well. When bound by ethanol, AMPAR pores open to allow an influx of chloride ions, which leads to hyperpolarization of cells. This in turn inhibits the generation of action potentials and a decrease in nerve signals to other cells, which significantly impacts animal behavior. In particular, ethanol binding NMDARs can greatly affect patients’ perception. Since NMDARs are highly concentrated in the prefrontal cortex, an area of the brain associated with choices and feelings, people who ingest ethanol lose inhibition and judgment.
Additionally, alcohol affects the release of dopamine, a chemical associated with feelings of pleasure. By enhancing molecular activity associated with dopamine-releasing cells in the ventral tegmental area of the brain, ethanol increases rewarding sensations and helps alleviate desensitization often associated with major depressive disorder.
Recent studies have also shown that alcohol affects endogenous peptide neurotransmitters (opioid peptides). These peptides, which act in the nucleus accumbens of the brain, structurally resemble morphine and also generate similar effects as the drug.
Current antidepressants operate on similar principles; monoamine oxidase inhibitors (MAOIs) inhibit the ability of the enzyme MAO to break down dopamine. However, these antidepressants treat milder forms of depression. Notably, ethanol, which affects dopamine release as well, seems to affect patients normally unresponsive to these antidepressants.
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