Blockade of mineralocorticoid and glucocorticoid receptors reverses stress-induced motor impairments.

AIM: Stress and glucocorticoids can influence movement performance and pathologies of the motor system. The classic notion assumes that the glucocorticoid receptor (GR) mediates the majority of stress-induced behavioral changes. Nevertheless, recent findings have attributed a more prominent role to the mineralocorticoid receptor (MR) in modulating behavior. The purpose of this study was to dissociate the impact of MR versus GR activation in movement and stress-associated motor disruption. METHODS: Groups of male and female rats were tested in skilled reaching and open field behavior and treated peri-orally with either agonists or antagonists for MR and GR, respectively. RESULTS: Selective acute activation of MR (aldosterone) and GR (dexamethasone) decreased movement success with a magnitude similar to stress-induced impairment in male and female animals. By contrast, antagonist treatment to block MR (RU-28318) or GR (Mifepristone, RU-486) prevented motor impairments caused by acute restraint stress or corticosterone treatment. Moreover, both antagonists reversed chronic stress- and glucocorticoid-induced motor impairments to values comparable to baseline levels. Higher success rates in treated animals were accompanied by improved performance of skilled limb movements. In addition, combined treatment with MR and GR antagonists had additive benefit on aim and advance towards the reaching target. CONCLUSION: These observations suggest that MR or GR equally influence motor system function with partially synergistic effects. Males and females show comparable responses to MR and GR activation or blockade. The need for balanced activation of MRs and GRs in motor control requires consideration in intervention strategies to improve performance in health and disease.

Predictable stress versus unpredictable stress: a comparison in a rodent model of stroke.

Previous studies have associated stress with poor outcome in individuals affected by stroke. It was suggested that the effects of stress depend on the stressor's type and strength. Here we compare the effects of chronic predictable restraint stress and chronic unpredictable variable stress on motor recovery after focal lesion in the rat motor cortex. Adult male rats were pre-trained and tested in skilled reaching and skilled walking tasks. Animals were assigned to daily treatments of either restraint stress or variable stress starting 1 week prior to lesion up to 2 weeks post-lesion. One group served as lesion only control. The results revealed a distinct pattern of recovery and compensation of skilled movement. Animals exposed to predictable restraint stress had significantly lower reaching success at both pre- and post-lesion time points, and higher error rates in skilled walking when compared to lesion controls. Overall, restraint stress induced more pronounced motor impairments prior to and after injury than variable stress. Variable stress increased the number of attempts required to grasp food pellets and changed movement pattern performance. By contrast, variable stress improved limb placement accuracy when compared to lesion controls. The behavioural changes were not accompanied by differences in infarct size. These findings are in agreement with other studies reporting that both chronic predicable restraint stress and unpredictable variable stress influence the course of recovery following stroke, however, restraint stress might affect stroke recovery through a different route than variable stress.