Drosophila study identifies genes relevant to consumption of drugs of abuse

Highfill CA, Baker BM, Stevens SD, Anholt RRH, Mackay TFC. Genetics of cocaine and methamphetamine consumption and preference in Drosophila melanogaster. PLoS Genet. 2019 May 20;15(5):e1007834. PMID: 31107875.

From the abstract: "Illicit use of psychostimulants, such as cocaine and methamphetamine, constitutes a significant public health problem. ... genetic factors that account for individual variation in susceptibility to substance abuse and addiction remain largely unknown. Drosophila melanogaster can serve as a translational model for studies on substance abuse, since flies have a dopamine transporter that can bind cocaine and methamphetamine, and exposure to these compounds elicits effects similar to those observed in people, suggesting conserved evolutionary mechanisms underlying drug responses. Here, we used the D. melanogaster Genetic Reference Panel to investigate the genetic basis for variation in psychostimulant drug consumption ... Quantification of natural genetic variation in voluntary consumption, preference, and change in consumption and preference over time for cocaine and methamphetamine uncovered significant genetic variation for all traits, including sex-, exposure- and drug-specific genetic variation. Genome wide association analyses identified both shared and drug-specific candidate genes ... "

Using the fly system to explore the role of glia in neurological diseases (review)

Zwarts L, Van Eijs F, Callaerts P. Glia in Drosophila behavior. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2015 Sep;201(9):879-93. PMID: 25336160.

From the abstract: "Glial cells constitute about 10% of the Drosophila nervous system. The development of genetic and molecular tools has helped greatly in defining different types of glia. ... We here summarize recent work describing the role of glia in normal behavior and in Drosophila models for neurological and behavioral disorders."

Cutting-edge techniques used in Drosophila help elucidate mechanisms of amphetamine transport in cells

Freyberg Z, Sonders MS, Aguilar JI, Hiranita T, Karam CS, Flores J, Pizzo AB, Zhang Y, Farino ZJ, Chen A, Martin CA, Kopajtic TA, Fei H, Hu G, Lin YY, Mosharov EV, McCabe BD, Freyberg R, Wimalasena K, Hsin LW, Sames D, Krantz DE, Katz JL, Sulzer D, Javitch JA. Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain. Nat Commun. 2016 Feb 16;7:10652. PMID: 26879809.

From the abstract: "Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration ... To study VMAT's role .. we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. ... we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects."

Flies & booze. Recent review.

Devineni AV, Heberlein U. The evolution of Drosophila melanogaster as a model for alcohol research. Annu Rev Neurosci. 2013 Jul 8;36:121-38. PMID: 23642133.

From the abstract:  "... we describe the ecological relationship between flies and ethanol, the effects of ethanol on fly development and behavior, the use of flies as a model for alcohol addiction, and the interaction between ethanol and social behavior. We discuss ... their utility to help decipher the mechanisms underlying the diverse effects of ethanol, including those that mediate ethanol dependence and addiction in humans."

New approach for study of learning and memory in flies. Relevance to disease-related study. Recent report.

The authors indicate relevance to "neurological pathologies such as Parkinson's disease, Alzheimer's disease, addiction, epilepsy and autism spectrum disorders."

Mejia M, Heghinian MD, Marí F, Godenschwege TA. New Tools for Targeted Disruption of Cholinergic Synaptic Transmission in Drosophila melanogaster. PLoS One. 2013 May 30;8(5):e64685. PMID: 23737994; PMCID: PMC3667824.