Methamphetamine causes anorexia in Drosophila melanogaster, exhausting metabolic reserves and contributing to mortality

• Published in: Journal of toxicological sciences Vol. 37; no. 4; pp. 773 - 790
• Main Authors: Walters, Kent R., Jr, Rupassara, S. Indu, Markelz, R.J. Cody, Leakey, Andrew D.B., Muir, William M., Pittendrigh, Barry R.
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 2012; Japan Science and Technology Agency
• Subjects: Animals; Anorexia; Anorexia - chemically induced; Anorexia - physiopathology; Diet; Dietary supplements; Diets; Drosophila melanogaster; Drosophila melanogaster - drug effects; Energy balance; Energy Intake; Energy Metabolism; Feeding Behavior; Food consumption; Glucaric Acid - administration & dosage; Glucose; Glycogen; Glycogen - analysis; Glycogen - metabolism; Locomotion; Locomotor activity; Male; Metabolic rate; Metabolism; Metabolites; Methamphetamine; Methamphetamine - toxicity; Mortality; Motor Activity - drug effects; Neurotoxicity; Oxidative Stress - drug effects; Respiration; Stress, Physiological; Sugar; Survival; Toxicity; Triglycerides; Triglycerides - analysis; Triglycerides - metabolism
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.37.773

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.