title: Effects of gender on locomotor sensitivity to amphetamine, body weight, and fat mass in regulator of G protein signaling 9 (RGS9) knockout mice.
abstract: Regulator of G-protein signaling (RGS) protein 9-2 is enriched in the striatum where it modulates dopamine and opioid receptor-mediated signaling. RGS9 knockout (KO) mice show increased psychostimulant-induced behavioral sensitization, as well as exhibit higher body weights and greater fat accumulation compared to wild-type (WT) littermates. In the present study, we found gender influences on each of these phenotypic characteristics. Female RGS9 KO mice exhibited greater locomotor sensitization to amphetamine (1.0mg/kg) treatment as compared to male RGS9 KO mice. Male RGS9 KO mice showed increased body weights as compared to male WT littermates, while no such differences were detected in female mice. Quantitative magnetic resonance showed that male RGS9 KO mice accumulated greater fat mass vs. WT littermates at 5months of age. Such observations could not be explained by increased caloric consumption since male and female RGS9 KO mice demonstrated equivalent daily food intake as compared to their respective WT littermates. Although indirect calorimetry methods found decreased oxygen consumption and carbon dioxide production during the 12-hour dark phase in male RGS9 KO vs. WT mice which are indicative of less energy expenditure, male RGS9 KO mice exhibited lower levels of locomotor activity during this period. Genotype had no effect on metabolic activities when KO and WT groups were compared under fasting vs. feeding treatments. In summary, these results highlight the importance of factoring gender into the experimental design since many studies conducted in RGS9 KO mice utilize locomotor activity as a measured outcome.
authors.affiliation: Department of Anatomy & Cell Biology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. Electronic address: pdwalker@med.wayne.edu.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Walker
authors.affiliation: College of Nursing, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Jarosz
authors.affiliation: Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Bouhamdan
authors.affiliation: Center for Integrative Metabolic and Endocrine Research, Department of Psychiatry & Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: MacKenzie
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology*; D002153:Calorimetry, Indirect; D002245:Carbon Dioxide / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D017440:Photoperiod; D020710:RGS Proteins / Q000172:deficiency* / Q000235:genetics; D012727:Sex Characteristics; D015398:Signal Transduction
chemical_list: D000697:Central Nervous System Stimulants; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D002245:Carbon Dioxide; D000661:Amphetamine
keywords: Basal ganglia; Homeostasis; Metabolism; Obesity; Sex-dependent; Substance abuse