Elsevier

Behavioural Brain Research

Volume 233, Issue 2, 1 August 2012, Pages 314-321
Behavioural Brain Research

Research report
The protective effects of voluntary exercise against the behavioral consequences of uncontrollable stress persist despite an increase in anxiety following forced cessation of exercise

https://doi.org/10.1016/j.bbr.2012.05.017Get rights and content

Abstract

Humans who exercise are less likely to suffer from stress-related mood disorders. Similarly, rats allowed voluntary access to running wheels have constrained corticosterone responses to mild stressors and are protected against several behavioral consequences of uncontrollable stress which resemble symptoms of human anxiety and depression, including exaggerated fear and deficits in shuttle box escape learning. Although exercise conveys clear stress resistance, the duration of time the protective effects of exercise against the behavioral consequences of uncontrollable stress persist following exercise cessation is unknown. The current studies investigated (1) whether exercise-induced stress resistance extends to social avoidance, another anxiety-like behavior elicited by uncontrollable stressor exposure, and (2) the duration of time the protective effects of exercise persist following forced cessation of exercise. Six weeks of wheel running constrained the increase in corticosterone elicited by social exploration testing, and prevented the reduction in social exploration, exaggerated shock-elicited fear, and deficits in escape learning produced by uncontrollable stress. The protective effect of voluntary exercise against stress-induced interference with escape learning persisted for 15 days, but was lost by 25 days, following cessation of exercise. An anxiogenic effect, as revealed by a reduction in social exploration and an increase in fear behavior immerged as a function of time following cessation of exercise. Results demonstrate that the protective effect of voluntary exercise against the behavioral consequences of uncontrollable stress extends to include social avoidance, and can persist for several days following exercise cessation despite an increase in anxiety produced by forced cessation of exercise.

Highlights

► Voluntary exercise prevents stress-induced social avoidance. ► Voluntary exercise attenuates mild stress-evoked increases in corticosterone. ► Forced cessation of exercise increases anxiety-like behaviors in rodents. ► Exercise-induced stress resistance endures following forced cessation of habitual exercise.

Introduction

Physical activity is one of the few environmental manipulations known to increase stress resistance. The stress resistance conferred by physical activity can be observed on many levels, from neuroendocrine [5], [11], [16], [41] and immunological [15], [17], [37], to behavioral [4], [9], [12], [20]. Laboratory rats allowed voluntary access to running wheels, for example, are protected against the development of anxiety- and depression-like behavioral consequences of exposure to a variety of stressors. Investigation of the powerful stress resistance produced by exercise could provide insight into novel therapeutic or preventative strategies, including the design of exercise programs optimal for mental health.

Exposure to uncontrollable stress produces a sequelae of behaviors in rodents which resemble symptoms of human stress-related psychiatric disorders. We have observed that rats allowed 6 weeks of voluntary access to running wheels are protected against many of these behavioral consequences of uncontrollable stress, including exaggerated fear conditioning [24], interference with shuttle box escape [9], [12], [24], and potentiation of the rewarding effects of morphine [39]. In addition to these behaviors, uncontrollable stress reduces social exploratory behavior [6], an effect argued to resemble anxiety [7]. Social avoidance produced by uncontrollable stress is dependent on hyperactivation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) [6]. Six weeks of wheel running constrains activity of DRN 5-HT neurons during uncontrollable stress [24]; therefore we might expect that 6 weeks of wheel running would also prevent the stress-induced reduction in social exploration. One goal of the current studies is to test this hypothesis.

To date, every animal study investigating the behavioral effects of exercise on anxiety- or depression-like behaviors of which we are aware have exposed the animals to stress or behavioral testing within 24 h following the last exercise bout. In our own experiments, rats are typically allowed access to their wheels before and after stressor exposure, and are tested for stress-induced behaviors the morning following a night of voluntary activity. It is unlikely that the protective effect of exercise against the behavioral consequences of stress is permanent. The second goal of the current studies, therefore, is to identify how long the protective effect of voluntary exercise persists following forced cessation of exercise. This knowledge could have important implications for the effects of human exercise participation, which is often discontinuous [34].

Section snippets

Animals

Male, Fischer F344 rats (total N = 161) were housed in a temperature (22 °C) and humidity-controlled environment and were maintained on a 12:12 h light/dark cycle (lights on 06:00–18:00). Experimental rats were 6–7 weeks old upon arrival to the animal colony. Juvenile rats used for the social exploration tests were housed in groups of 6 and were 28 ± 2 days old (90–100 g) at the time of testing. Animals acclimatized to these housing conditions for 1 week prior to any experimental manipulation.

Body weight and running behavior

Average body weight gain over the course of the experiment is shown in Fig. 1A. Rats in the Sedentary and Run groups weighed similar amounts prior to the start of voluntary running. All rats gained weight over time (F (6, 168) = 812.7; p < 0.0001), but exercised rats gained less weight than sedentary rats (F (6, 168) = 16.6; p < 0.0001). Average weekly distance run is shown in Fig. 1B. Weekly running distance increased steadily over the course of the experiment (F (5, 70) = 15.3; p < 0.0001) from 8.1 ± 0.92 

Discussion

Here we report the novel finding that the protective effect of voluntary exercise against the behavioral consequences of uncontrollable stress extends to include the anxiety-like reduction in social exploratory behavior. Moreover, exercise-induced resistance against the behavioral consequences of uncontrollable stress, including the reduction in social exploration, exaggerated fear, and the shuttle box escape deficit, persists between 15 and 25 days following forced exercise cessation despite

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