The consequences of uncontrollable stress are sensitive to duration of prior wheel running.

The behavioral consequences of uncontrollable stress, or learned helplessness (LH) behaviors, are thought to involve hyperactivity of serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). Other brain regions implicated in LH and capable of affecting 5-HT systems, such as the bed nucleus of the stria terminalis (BNST), amygdala, and habenula, could contribute to DRN 5-HT hyperactivity during uncontrollable stress. Six weeks of wheel running prevents LH and attenuates uncontrollable stress-induced c-Fos expression in DRN 5-HT neurons, although the duration of wheel running necessary for these effects is unknown. In the current study, 6 but not 3, weeks of wheel running blocked the shuttle box escape deficit and exaggerated fear produced by uncontrollable tail shock in sedentary rats. Corresponding to the duration-dependent effects of wheel running on LH behaviors, 6 weeks of wheel running was required to attenuate uncontrollable stress-induced 5-HT neural activity, indexed by c-Fos protein expression, in the DRN and c-Fos expression in the lateral ventral region of the BNST. Wheel running, regardless of duration, did not affect c-Fos expression anywhere in the amygdala or habenula. These data indicate that the behavioral effects of uncontrollable stress are sensitive to the duration of prior physical activity and are consistent with the hypothesis that attenuation of DRN 5-HT activity contributes to the prevention of LH by wheel running. The potential role of the BNST in the prevention of LH by wheel running is discussed.