That alcohol has an addictive dimension is well-known, and the effects of this particularly deleterious aspect have been well-documented. However, it is not well known how alcohol produces its addictive effects, given the fact that it’s naturally a very weak reinforcer (i.e., it doesn’t directly work on the brain’s reward centers, as do, for example, cocaine and tobacco). This poses a serious problem in terms of effectively combating alcohol’s addictive nature.
To better understand the atypical nature of alcohol addiction, an international team of researchers has been looking at how chronic alcohol consumption alters extracellular space geometry and the diffusion on neurotransmitters in the brain.
While we typically think of neurotransmitters as existing in the synapse that connects two neurons, many transmitters—whether by design or dysfunction—escape this region and act on the brain more generally, not unlike hormones. A large part of what determines the extent and rate of neurotransmitter diffusion in the brain is the geometry or layout of the extracellular space (everything outside the neurons).
The researchers examined the brains of 84 male rats and 84 adult human males. Their results shed new light on the relationship between alcohol and addiction, with important implications for future research and treatment. Chronic ethanol consumption was shown to increase mean diffusion in the brains of both rats and humans.
The researchers provide strong evidence indicating that this increased diffusion is due in part to reduced ‘parenchyma tortuosity’—a measure of how ‘maze-like’ the extracellular space in the brain is. The more complex and dense this maze, the less quickly and extensively neurotransmitters can diffuse to other parts of the brain.
Glial cells play a large role in tortuosity and overall extracellular geometry, as they are partly responsible for the structure and maintenance of the extracellular space. Both humans and rats showed a significant decrease in microglial markers following chronic alcohol consumption, making them a prime candidate for the mediator between alcoholism and increased neurotransmitter diffusion.
How does this relate to addiction? The authors hypothesize (and model mathematically) that alterations in tortuosity would enable reward-related neurotransmitters like dopamine to reach and thus differentially influence regions of the brain they may not otherwise or extensively impact.
This has important implications for understanding alcohol addiction and may explain in part the “slow onset but potent addictive effect of alcohol.” Other mechanisms may also be affected by increased diffusion, like waste removal and structural plasticity.
Alcoholism is one of the most destructive and costly health crises in the world, and yet its mechanisms are still poorly understood. Research like the present study is essential to better understanding and thus combatting its deleterious effects at individual, community and national levels.
The study, “Chronic alcohol consumption alters extracellular space geometry and transmitter diffusion in the brain”, was published in Science Advances.
