LAUSR

Consumption of alcohol creates a sense of euphoria, reduces inhibition, and increases sociability and impulsivity (1). The age at which alcohol is first experienced is a key factor contributing to the likelihood to misuse alcohol (2). However, the impacts of the first experience of alcohol on the molecules in the brain at these key developmental stages are not well understood. Knabbe et al. (3) endeavored to address the neuromolecular alterations resulting from acute alcohol by combining hippocampal proteomics with somatosensory and motor cortex protein, dendrite, axon, and mitochondrial analysis in adolescent mice. Evidence from this array of preparations led to the hypothesis that alcohol disrupted mitochondrial trafficking, and using Drosophila they demonstrated a functional role for mitochondrial trafficking in cue-induced alcohol preference. The cross-assay and cross-species approach outlined in Knabbe et al. (3) proved to be an effective way of discovering how alcohol hijacks brain mechanisms. Animals from flies to humans maintain functionally consistent neurotransmitter systems, neural circuit mechanisms, and molecular pathways underlying reward (4). Flies and mice also demonstrate behavioral responses to the pharmacological properties of alcohol that look remarkably similar to those in humans, highlighting the conserved neurobiological basis of alcohol on the brain (5). Although the similarity in brain structure and genetic sequences between mice and humans allows us to easily intuit the application of results in mice to humans, the observation that alcohol affected similar proteins across different brain regions speaks to the broad effects of alcohol on the brain (3). This also allowed the authors to take advantage of multiple assays to study mechanism across several levels of analysis to get a detailed understanding of the underlying cell biology (Fig. 1). Ultimately this led to the discovery of a role for mitochondrial trafficking in how alcohol affects neuronal activity, structural plasticity, and behavior (3). The conservation in mechanism across several brain regions in mice also hinted that this role for alcohol may translate across species. Indeed, the authors demonstrated a functional role for mitochondrial trafficking in cueinduced alcohol preference in Drosophila by in vivo manipulation of mitochondria trafficking in specific cell types using sophisticated genetic tools (6) (Fig. 1). The remarkable convergence upon a single mechanism by leveraging several assays across brain regions and species demonstrates the effectiveness of interdisciplinary and collaborative work.