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.

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