Single Alcohol Consumption Event Can Lay Groundwork for Addiction

Researchers in Germany have found that even one alcoholic drink can permanently alter neuronal structure of fruit fly Drosophila melanogaster and lay the groundwork for alcohol addiction. The findings suggest the structure of the synapses and dynamics of mitochondria are particularly influenced by alcohol.

Most scientific research has examined the effects of chronic alcohol consumption on the hippocampus, the control center of the brain, and little is known about the acute neuronal interactions of critical risk factors, such as a first alcohol intoxication at an early age. But the new study, published recently in Proceedings of the National Academy of Sciences andconducted by a team from the Universities of Cologne, Mannheim and Heidelberg, looked at which changes in the brain accompany the transition from sporadic drinking to chronic alcohol abuse. 

“We set out to discover ethanol-dependent molecular changes,” says Henrike Scholz, professor at the University of Cologne. “These, in turn, provide the basis for permanent cellular changes following a single acute ethanol intoxication. The effects of a single alcohol administration were examined at the molecular, cellular and behavioral levels.”

The working hypothesis was that, similar to the formation of memory after a single lesson, a single administration of ethanol would form a positive association with alcohol. Using the genetic model system of the fruit fly Drosophila melanogaster, Scholz and colleagues Michèle Tegtmeier and Michael Berger showed that changes in the migration of mitochondria in the synapses reduce the rewarding effect of alcohol. This suggests that even a single consumption event can lay the foundation for alcohol addiction.

The team tested its hypothesis using research in fruit flies and mouse models and found ethanol-induced changes in two areas: mitochondrial dynamics and the balance between synapses in neurons. Mitochondria supply cells and especially nerve cells with energy. In order to optimally deliver the energy to the cells, mitochondria move, but this movement was disturbed in the cells treated with ethanol. The chemical balance between certain synapses was also disturbed. These changes remained permanent and were confirmed by behavioral changes in the animals, with mice and fruit flies showing increased alcohol consumption and alcohol relapse later in life.

The morphological remodelling of neurons is a well-known basis for learning and memory. Such cellular plasticity mechanisms are also thought to be at the core of the formation of associative memories for drug-related rewards. Therefore, some of the observed morphological changes may influence ethanol-related memory formation.

Together with the migration of mitochondria in neurons, which are also important for synaptic transmission and plasticity, the researchers speculate that these ethanol-dependent cellular changes are critical for the development of addictive behaviors. “It is remarkable that the cellular processes contributing to such complex reward behavior are conserved across species, suggesting a similar role in humans,” Scholz says. “It could be a possible general cellular process essential for learning and memory.”

Both of the observed mechanisms could explain findings in mice that a single intoxication experience can increase alcohol consumption and alcohol relapse later in life. “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,” Scholz adds. “This means that identifying lasting ethanol-dependent changes is an important first step in understanding how acute drinking can turn into chronic alcohol abuse.”