Sexual Dimorphism of Behavioral Response to Dopamine Modulation in Drosophila

Abstract

IntroductionDespite considerable evidence that women are more vulnerable to addiction than men, biomedical research has been performed almost exclusively in males, and the results assumed to apply equally to men and women. Recent NIH policy regarding inclusion of sex as a biological variable is contributing to more proportional evaluation and greater translational value of future publications, but the current body of literature contains very little regarding sex differences in Drosophila melanogaster response to psychostimulants. While studying the contributions of the serotonergic system on psychostimulant response in Drosophila using DREADD technology and the Drosophila Activity Monitoring System (DAMS), we found sexually dimorphic behavioral responses to methamphetamine in numerous strains of Drosophila. Although tangential to our initial objective, we explored the influence of sex as a biological variable on locomotor response to dopaminergic modulation.ObjectiveTo describe sexually dimorphic behavioral responses to dopaminergic modulation in several strains of Drosophila.MethodsRecently eclosed, non‐entrained, male and female flies (n=16/group) were fed 5 mM methamphetamine in vehicle medium or vehicle medium (10% sucrose, 1% agarose gel) and monitored in the DAMS under constant light conditions for one week. Beam breaks recorded by the DAMS were summed into one‐hour bins and group means were calculated. Group means were then evaluated individually with repeat measures ANOVA, and included in a meta‐analysis using sex (male, female) as subgroups. A separate experiment used two wild‐type strains with established locomotor differences to evaluate the influence of sex and strain on locomotor response to 3 mM DL‐α‐Methyltyrosine (metyrosine), a tyrosine 3‐monooxygenase inhibitor. Metyrosine administration and DAMS monitoring was performed as described above, and group means were then evaluated using repeat measures ANOVA.ResultsMale and female flies displayed significantly increased locomotor activity than control flies when fed methamphetamine. Female flies of all strains displayed significantly higher baseline activity than male flies, but significantly less methamphetamine‐induced increases in locomotor activity than male flies. While male flies fed methamphetamine displayed persistent, steady increases in locomotor activity throughout the studies, female flies fed methamphetamine displayed progressively smaller locomotor differences Days 4–7, and no behavioral differences from control flies on Day 8.Male and female flies displayed significantly decreased decreased locomotor activity than control flies when fed metyrosine. Female flies of both strains displayed significantly higher baseline activity than male flies, but significantly more metyrosine‐induced decreases in locomotor activity than male flies. Metyrosine‐induced reductions in locomotor activity were persistent and steady for both male and female flies throughout the duration of the experiment.Support or Funding InformationThis work was supported in whole by the National Institute on Drug Abuse of the National Institutes of Health under award number R21DA039462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.