Abstract
Rationale
Women are more sensitive than men to psychostimulants and progress from initial use to drug addiction more quickly. The mouse has been an under-utilized model to study sex differences in psychostimulant action. Mice could serve as an ideal genetically tractable model for mechanistic studies into sex and hormone effects on psychostimulant behavior.
Objectives
The objective of this study was to characterize psychostimulant effects in male and female mice with a combination of automated data collection and behavioral observation.
Methods
Male and female C57BL/6 mice (Charles River) were given a single dose or sequential ascending binge doses of d-amphetamine (AMPH) or cocaine (COC). Behavior was assessed in open field chambers using both automated photobeam interruptions and behavioral observations. Brain psychostimulant concentrations were determined at the time of maximum behavioral stimulation.
Results
Psychostimulants induced behavioral activation in mice including both increased locomotion as detected with an automated system and a sequence of behaviors progressing from stereotyped sniffing at low doses to patterned locomotion and rearing at high doses. Females exhibited more patterned locomotion and a shift towards higher behavior scores after either psychostimulant despite having lower AMPH and equivalent COC brain levels as males.
Conclusions
Female C57BL/6 mice exhibit enhanced psychostimulant-induced behavior compared to males, similar to reports in rats. The combination of automated behavioral measures and behavioral observation was essential for verifying the existence of these differences. These results indicate the importance of testing both sexes when characterizing genetically manipulated mice to control for potential sex-specific effects.
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Acknowledgments
The authors thank the lab of Dr. David Moody at the Center for Human Toxicology, University of Utah for the assessment of psychostimulant concentrations. We also thank Dr. Nicole Schramm-Sapyta, Andrew Arrant, Suzanne Frisbee, Caroline Biskup, and Alex Jaeger for assistance with this study. All experiments in this study comply with current United States laws.
Funding
This work was supported by the National Institute of Drug Abuse [Contract N01DA-9-7767 with Dr. Moody at the University of Utah and Grant DA009079 to Dr. Kuhn].
Conflict of interest
The authors have no conflicts to declare.
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Van Swearingen, A.E.D., Walker, Q.D. & Kuhn, C.M. Sex differences in novelty- and psychostimulant-induced behaviors of C57BL/6 mice. Psychopharmacology 225, 707–718 (2013). https://doi.org/10.1007/s00213-012-2860-4
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DOI: https://doi.org/10.1007/s00213-012-2860-4