Prof. Denis B. Rosemberg - I IZN Web Conference

Title: Understanding the neurobehavioral responses of alcohol abuse in zebrafish: influence of the serotonergic system and mitochondrial bioenergetics.

Abstract: Alcohol abuse constitutes a public health problem with increased levels of mortality and morbidity due to the manifestation of alcohol-related disorders. Although the acute and chronic responses of ethanol administration have been extensively described, the neural mechanisms underlying the behavioral phenotypes observed still remain to be elucidated. Because the zebrafish (Danio rerio) presents a high degree of genetic conservation, evolutionarily conserved neurophysiology, and sophisticated behaviors, this species is a suitable model organism in behavioral neuropsychopharmacology. Moreover, similar to humans, the behavioral effects of ethanol in zebrafish vary in a concentration- and time-dependent manner. Acutely, low ethanol concentrations promote anxiolysis and increase aggression, while high concentrations induce a depressant-like effect and oxidative stress in the brain. Importantly, repeated alcohol exposure can promote anxiogenic-like effects, as well as lipid peroxidation in brain tissue. In this lecture, I will discuss how the serotonergic system and brain mitochondrial bioenergetics play a role in both acute and chronic effects of ethanol in zebrafish. Using the mirror-induced aggression test, we observed a putative involvement of 5HT2A receptors in the aggressive responses of 0.25% ethanol (v/v) since the administration of pCPA and ketanserin blocked ethanol-induced effects, while a 5HT2A agonist mimicked the aggression. Although no effects of the serotonergic system were verified in the hypolocomotion following 1.0% ethanol (v/v), 5HT1B receptors influence 0.5% ethanol-induced anxiolysis. The measurement of mitochondrial function by high-resolution respirometry assay showed that 1.0% ethanol (v/v) acutely stimulates complex I and oxidative phosphorylation. Conversely, 1.0% ethanol (v/v) chronically decreases complex II-mediated electron transport, suggesting an involvement of mitochondrial bioenergetics in oxidative responses. Overall, the behavioral effects of ethanol in zebrafish are mediated, at least partially, by changes in the serotonergic system and mitochondrial function. Taken together, I will emphasize how the use of zebrafish models can be fruitful to assess the underlying neural mechanisms associated to the behavioral effects of alcohol in a translational perspective.