Blockade of Mineralocorticoid and Glucocorticoid Receptors Reverses Stress-Induced Motor Impairments

Abstract

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.

Environmental Intervention as a Therapy for Adverse Programming by Ancestral Stress

“…The longitudinal findings revealed that ancestral stress favors precocious onset of elevated motor activity and risk assessment behaviours in response to the novel and slightly aversive environments of open field and elevated plus maze. Both tests are standard assessments of anxiety-like behaviour and response to novelty4344. The indication that ancestral stress enhances the vulnerability to hyperactive and anxiety-like behaviours agrees with findings made in prenatally stressed animals45464748.…”

“…The open field task allows quantification of exploration of an aversive open arena4344. The open field task was conducted using the VersaMax Legacy Open Field system (Omnitech Electronics, Inc., Dartmouth, NS, Canada; Fig.…”

Behavioral and molecular alterations in mice resulting from chronic treatment with dexamethasone: Relevance to depression

“…Thus, the data obtained in the present study indicate that locomotor activity was not impaired in DEX-treated mice. Previous studies in rats have shown that DEX significantly decreased movement success as measured by the OF test, with a magnitude similar to stress-induced impairment in animals (Jadavji et al, 2011). Liu et al (2012) tested a rat model of depression elicited by prenatal exposure to DEX, and their results indicate that adult offspring rats exhibited a decreased number of both rearings and distance traveled in the OF.…”

Lifespan Psychomotor Behaviour Profiles of Multigenerational Prenatal Stress and Artificial Food Dye Effects in Rats

“…In this experiment, pregnant rat dams were exposed to a semi-random combination of restraint and swim stress, which may represent an ecologically valid rat model of moderate stress [7],[19] with effects on motor behaviour [21]–[23]. We used the open field task, a standard test to effectively assess motor activity and anxiety-related behaviour [24]–[25].…”

“…The animals were tested using an open field task [22],[23], at P 50, 3 months, 7 months, and 13 months of age. The open field task allows the quantification of motor activity, anxiety-like behaviours, and exploration in an open arena.…”