Dheas And Glutamategetec System In Stress Response

Dehydroepiandosterone sulfate (DHEAS), a neuroactive steroid, has been demonstrated to bind to sigmal receptor, and it has antidepressive effects in the forced swimming test. We used the conditioned fear stress (CFS), which is useful for investigating the pathogenesis of mood disorders. DHEAS and trilostane (3 b -hydrosteroid dehydrogenase (3 b-HSD) specific inhibitor) attenuated the CFS response in mice and the effects antagonized by NE-100, a sigmal receptor antagonist. In contrary, fluorocitrate (a glia metabolism inhibitor) enhance the CFS response, the effect being attenuated by DHEAS. Interestingly, the number of apoptotic cells in the brain of mice showing CFS was increased, and DHEAS can prevent the enhancement of apoptotic cells. These findings suggest that the imbalance of neuroactive steroid and the expression of apoptosis play an important role in CFS response. In a word, the use of DHEAS is a novel therapeutic approach for at least some mood disorders.The present study was investigated the behavioral effects of phencyclidine (PCP) on stress responses in mice, since PCP has been reported to induced schizophrenic-like symptoms and schizophrenic patients has been demonstrated to sensitive to the stressful event. The forced swimming regards as acute inescapable physical stress, produces immobility in rodents. Chronic treatment with PCP enhanced the immobility in the forced swimming test in mice. The enhanced effect of PCP was attenuated by atypical antipsychotics and glycine agonist, but not by the typical antipsychotics. In the conditioned fear stress (CFS) test, a psychological stress test, repeated PCP treatment enhanced the CFS response. Glycine agonists but not typical and atypical antipsychotics attenuated the enhancement induced by PCP. In mice pretreated with PCP repeatedly, the expression of N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A, and NR2B) protein in the nucleus accumbens and c-Fos protein in the prefrontal cortex and nucleus accombens were increased. These findings suggest that such effect of PCP on both stress responses are involved in glutamatergic systems.