METYRAPONE PRETREATMENT PREVENTS THE BEHAVIORAL AND NEUROCHEMICAL SEQUELAE INDUCED BY STRESS

In the present study, we examined the effect of metyrapone, an inhibit or of corticosterone (CS) synthesis, on the behavioral and neurochemic al sequelae induced by a brief restraint session. A 15-min stress peri od induced an anxiogenic-like behavior on the elevated plus-maze (EPM) , which was reversed with metyrapone (75 mg/kg i.p.) injected 3 h prio r to the stress event. It was further demonstrated that metyrapone pre treatment normalized the decrease in maximal chloride uptake following GABA stimulation observed in brain cortex tissue obtained from animal s exposed to both restraint and the EPM. In addition, plasma CS levels were assessed both after restraint and following EPM exposure. Furthe rmore, the administration of both CS (2.5 mg/kg s.c. at a dose that mi mics CS levels induced by restraint) or dexamethasone (DEXA, 1.25 mu g /kg s.c) resulted in an anxiogenic response in the EPM comparable to t hat induced by restraint. Taken together, all these evidence suggest t hat CS released in response to stress seems to be associated with func tional changes at the GABAergic supramolecular complex which could und erlie the enhanced anxiety observed following the exposure to an avers ive experience. (C) 1998 Elsevier Science B.V. All rights reserved.