title: Methamphetamine causes anorexia in Drosophila melanogaster, exhausting metabolic reserves and contributing to mortality.
abstract: Methamphetamine (MA) appears to produce neurotoxic effects, in part, through disruptions of energy metabolism. A recent study of the whole-body proteome of Drosophila melanogaster showed many changes in energy metabolism-related proteins, leading us to hypothesize that MA toxicity may cause whole-body disruptions of energy metabolism. To test this, we monitored the response of energy reserves and other metabolites to MA-exposure with and without the addition of dietary glucose. We also monitored changes in feeding behavior, locomotor activity and respiration rates associated with MA-exposure to investigate how MA affects energy balance. We observed that glycogen and triglyceride levels decreased dramatically within 48 hr of MA-exposure, indicating a strongly negative caloric balance. Behavioral assays revealed that MA-treated flies decreased food consumption by 60-80% and exhibited a 2-fold increase in locomotion. Caloric expenditure decreased with MA-exposure, apparently due to a compensatory decrease in resting metabolism, showing that anorexia was the primary driver of the negative caloric balance. Additionally, we observed that glucose supplementation of MA-containing diet increased glycogen reserves by 44% at 48 hr, leading to a commensurate increase in survivorship. We conclude that dietary sugar supplementation enhances survivorship by partially compensating for decreased caloric intake resulting from MA-induced anorexia. The observation that MA produces similar behavioral changes in Drosophila and humans, i.e. increased locomotor activity and anorexia, further supports the use of Drosophila as a model organism for the study of the effects of MA.
authors.affiliation: Department of Entomology, 516/518 Morrill Hall, University of Illinois, Urbana, IL 61801, USA. krwaltersjr@gmail.com
authors.forename: Kent R
authors.initials: KR
authors.lastname: Walters
authors.forename: S Indu
authors.initials: SI
authors.lastname: Rupassara
authors.forename: R J Cody
authors.initials: RJ
authors.lastname: Markelz
authors.forename: Andrew D B
authors.initials: AD
authors.lastname: Leakey
authors.forename: William M
authors.initials: WM
authors.lastname: Muir
authors.forename: Barry R
authors.initials: BR
authors.lastname: Pittendrigh
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000503:physiopathology*; D004032:Diet; D004331:Drosophila melanogaster / Q000187:drug effects*; D002149:Energy Intake; D004734:Energy Metabolism; D005247:Feeding Behavior; D005937:Glucaric Acid / Q000008:administration & dosage; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D013312:Stress, Physiological; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
chemical_list: D014280:Triglycerides; D008694:Methamphetamine; D006003:Glycogen; D005937:Glucaric Acid