Female rats are more responsive than are males to the protective effects of voluntary physical activity against the behavioral consequences of inescapable stress

Abstract

Common stress-related mental health disorders affect women more than men. Physical activity can provide protection against the development of future stress-related mental health disorders (i.e. stress resistance) in both sexes, but whether there are sex differences in exercise-induced stress resistance is unknown. We have previously observed that voluntary wheel running (VWR) protects both female and male rats against the anxiety- and exaggerated fear-like behavioral effects of inescapable stress, but the time-course and magnitude of VWR-induced stress resilience has not been compared between sexes. The goal of the current study was to determine whether there are sex differences in the time-course and magnitude of exercise-induced stress resistance. In adult female and male Sprague Dawley rats, 6 weeks of VWR produced robust protection against stress-induced social avoidance and exaggerated fear. The magnitude of stress protection was similar between the sexes and was independent of reactivity to shock, general locomotor activity, and circulating corticosterone. Interestingly, 3 weeks of VWR prevented both stress-induced social avoidance and exaggerated fear in females but only prevented stress-induced social avoidance in males. Ovariectomy altered wheel-running behavior in females such that it resembled that of males, however; 3 weeks of VWR still protected females against behavioral consequences of stress regardless of the absence of ovaries. These data indicate that female Sprague Dawley rats are more responsive to exercise-induced stress resistance than are males.

GRAPHICAL ABSTRACT

HIGHLIGHTS

• The duration of wheel running required to enable stress resistance differs between the sexes in a behavior-dependent manner.

• Wheel running enables rapid protection against stress-induced social avoidance in both male and female Sprague Dawley rats.

• Wheel running enables protection against stress-induced exaggerated fear more readily in female Sprague Dawley rats compared to males.

• Ovarian hormones are not necessary for stress-protection produced by 3 weeks of wheel running in female Sprague Dawley rats.

Keywords:

• Exercise
• sex differences
• wheel running
• stress resilience
• ovarian hormones
• anxiety
• fear
• serotonin

Acknowledgements

We are grateful to Dr. Matthew Frank for assisting with corticosterone measurements.

Author contributions

Margaret Tanner: conceptualization, experimentation, analysis, writing the manuscript; Alyssa Hohorst: conceptualization, experimentation, analysis; Simone Mellert: experimentation, analysis; Esteban Loetz: experimentation; Michael Baratta: conceptualization, editing manuscript; Benjamin Greenwood: conceptualization, analysis, writing the manuscript. All authors approved the submitted manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data will be made available on request.

Additional information

Funding

These studies were funded by the National Institutes of Health (R01MH125898).

Notes on contributors

Margaret K. Tanner

Margaret K. Tanner

received her PhD in Integrative Biology from the University of Colorado Denver, USA. She is currently a post-doctoral fellow in the Behavioral Exercise Neuroscience laboratory at the University of Colorado Denver.

Alyssa A. Hohorst

Alyssa A. Hohorst

is a doctoral candidate at the University of Colorado Denver, USA.

Simone M. Mellert

Simone M. Mellert

is a doctoral candidate at the University of Colorado Denver, USA.

Esteban C. Loetz

Esteban C. Loetz

is a professional research assistant in the Behavioral Exercise Neuroscience laboratory at the University of Colorado Denver, USA.

Michael V. Baratta

Michael V. Baratta

is an Assistant Professor in the Department of Psychology and Neuroscience at the University of Colorado Boulder, USA. His lab studies the neural basis of stress resilience.

Benjamin N. Greenwood

Benjamin N. Greenwood

is an Associate Professor in the Department of Psychology at the University of Colorado Denver, USA. He is director of the Behavioral Exercise Neuroscience laboratory.