A single exposure to ethanol produces lasting alterations to neurons of both mice and fruit flies, resulting in synaptic remodeling within the reward circuit of the brain, new research reveals. In the journal PNAS, the study suggests that just one alcoholic drink may prime the brain to become addicted to booze further down the line.
Little is known about how the neuronal processes that mediate the transition from occasional drinking to full-blown alcoholism. To learn more about this slippery slope, the study authors set out to examine the molecular, cellular, and behavioral effects of a single dose of alcohol in two species that are often used as models for studying the human brain.
Using quantitative mass spectrometry, the researchers screened over 2,000 hippocampal proteins in the brains of mice following exposure to ethanol. In total, they identified 72 proteins that were dramatically altered by alcohol use.
For instance, changes to the proteins MAP6 and ankyrin-G resulted in a shortening of a key section of neuronal connecting arms – known as the axon initial segment – for at least 24 hours after exposure. In addition, the researchers observed a pronounced increase in the movement of mitochondria into mouse neurons that were treated with ethanol.
Because mitochondria provide nerve cells with energy, this increase in migration is likely to have a substantial impact on the way that these neurons function. This, combined with the morphological alterations seen in nerve cells exposed to ethanol, suggests that a single administration of alcohol may produce dramatic changes within the brain that could lay the foundations for alcoholism
“Some of the ethanol-dependent morphological changes we observed could potentially influence ethanol-related memory formation by distorting the synaptic connectivity balance,” explain the study authors.
To test this theory, they sought to reverse these cellular impacts in fruit flies that had developed a preference for ethanol. By inhibiting the proteins that control the migration of mitochondria into dopamine neurons, the researchers eliminated the animals’ dependence on alcohol.
Such a finding would appear to confirm the hypothesis that the cellular changes observed following a single exposure to ethanol do indeed underlie the neurology of addiction. While more research is needed in order to determine whether this applies to humans, it is noteworthy that the development of ethanol addiction in both fruit flies and humans is dependent upon dopamine neurons.
"It is remarkable that the cellular processes contributing to such complex reward behavior are conserved across species, suggesting a similar role in humans," explained study author Henrike Scholz in a statement. "These mechanisms may even be relevant to the observation in humans that the first alcohol intoxication at an early age is a critical risk factor for later alcohol intoxication and the development of alcohol addiction.”
"This means that identifying lasting ethanol-dependent changes is an important first step in understanding how acute drinking can turn into chronic alcohol abuse."