An automated direct assay system using high performance liquid chromatography was developed for the measurement of RU38486 and its three metabolites (RU42698, RU42848, RU42633) in human serum. Serum concentrations of these compounds were measured up to 144 h following single oral administration of 200 (200 mg group, n = 3) or 400 mg (400 mg group, n = 3) of RU38486 to healthy female volunteers....

We studied the effects of oral administration of RU38486, a potent and selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose-6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltran...

Association between the reward caused by consuming drugs and the context in which they are consumed is essential in the formation of morphine-induced conditioned place preference (CPP). Glucocorticoid receptor (GRs) activation in different regions of the brain affects reward-based reinforcement and memory processing. A wide array of studies have demonstrated that blockage of GRs in some brain a...

Pregnant rats were injected with 3H RU38486 into the uterine cavity on day 2, 4, 5 and 8 of pregnancy. Before implantation, the saturable RU binding increased significantly (day 2 vs. 4; 30.0 +/- 2.3 vs. 640.0 +/- 17.9 dpm/g, p less than 0.001). After implantation, the binding became higher at the nidation site (implantation vs. non-implantation site; 1156.1 +/- 237.1 vs. 595.0 +/- 24.3, p less...

We have examined acute effects of corticosterone (CORT) on N-methyl-D-aspartate (NMDA) receptor-mediated Ca signals in adult mouse hippocampal slices. We found so far that the 30 min preincubation of CORT induced a significant decrease of the peak amplitude of NMDAinduced Ca elevation in the CA1 region. The membrane non-permeable bovine serum albumin-conjugated CORT also induced a similar effec...

Elevated levels of corticosteroid hormones, presumably occupying both mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs), have been reported to impair synaptic plasticity in the hippocampus as well as the acquisition of hippocampus-dependent memories. In contrast, recent evidence suggests that activation of MRs enhance cognitive functions. To clarify the roles of different ste...

We have examined acute effects of corticosterone (CORT) on N-methyl-D-aspartate (NMDA) receptor-mediated Ca signals in adult mouse hippocampal slices. We found so far that the 30 min preincubation of CORT induced a significant decrease of the peak amplitude of NMDAinduced Ca elevation in the CA1 region. The membrane non-permeable bovine serum albumin-conjugated CORT also induced a similar effec...

Corticosteroid hormones are thought to promote optimal behavioral adaptation under fearful conditions, primarily via glucocorticoid receptors (GRs). Here, we examined - using pharmacological and genetic approaches in mice - if mineralocorticoid receptors (MRs) also play a role in fearful memory formation. As expected, administration of the GR-antagonist RU38486 prior to training in a fear condi...

The stress response is essential to the survival of all species as it maintains internal equilibrium and allows organisms to respond to threats in the environment. Most stress research has focused on the detrimental impacts of stress on cognition and behavior. Reversal learning, which requires a change in response strategy based on one dimension of the stimuli, is one type of behavioral flexibi...