Co-administration of the glucocorticoid receptor antagonist RU486 with the NMDA receptor antagonist MK-801 in male Sprague Dawley rats unexpectedly enhanced rather than blocked the development of locomotor sensitisation. Both RU486 and MK-801 individually raised plasma corticosterone levels, and the combination further increased them. RU486 also elevated dopamine, DOPAC, and HVA in nucleus accumbens tissue. The findings indicate that glucocorticoids play a divergent role in sensitisation to MK-801 compared to other psychostimulants.
Cognitive flexibility, the ability to adapt behavior to changing rules, is impaired in schizophrenia and predicts functional outcomes, yet antipsychotics do not improve it. A novel dynamic strategy shifting task (DSST) was optimized in operant chambers for rats, requiring a minimum of 6 correct consecutive responses to switch between spatial and non-spatial rules. Testing 84 Sprague Dawley rats with acute ketamine (0, 3, 10 mg/kg) showed fewer premature and more perseverant responses to initiate trials. Ketamine significantly improved reversal of a non-spatial visual discrimination rule but had no effect on spatial visual or response discrimination rules. The DSST provides a rapid assay for distinct forms of cognitive flexibility relevant to neuropsychiatric conditions.