Chronic treatment with desipramine: effect on endocrine and behavioral responses induced by inescapable stress.

Inescapable shock (IS) exposure induces behavioral inactivity, related to behavioral alterations in subsequent tests (i.e. escape failure during shuttle box task). Previous studies have demonstrated that various antidepressant treatments administered either before or after IS exposure reversed these behavioral deficits. Recently, we demonstrated corticosterone (CS) involvement both in inactivity performance during IS and in the number of escape failures in a shuttle box task. In the present study, we analyzed the effects of chronic desipramine (DMI) treatment administered before or after IS exposure on the dynamics of changes in serum CS concentration after both IS and shuttle box task, to explore a possible relationship between the hormonal response and the reversion of the behavioral induced by DMI. DMI (10 mg/kg intraperitoneally i.p.) administered during 6 consecutive days before IS reduced release and inactivity induced by this aversive experience. Two days later, when these DMI-treated rats were submitted to a shuttle box task, a reduction in CS release and IS-induced escape failures were observed as compared with saline-treated rats. Besides, in animals without IS experience, the pretreatment with DMI did not modify either the pattern of CS secretion or the percentage of escape failures as compared with saline-injected rats. On the other hand, CS values of rats treated with DMI during 6 consecutive days after IS exposure recovered to resting controls levels within 60 min post-shuttle box task, exhibiting fewer escape failures; unlike saline-treated, IS-exposed rats, which retained persistently elevated levels of CS (during the post-task sampling interval) a showed a high percentage of escape failures. Thus, chronic DMI administration before IS attenuated CS secretion and prevented the onset and expression of behavioral deficits induced by uncontrollable stressors. However, when it was administered after IS, it induced an increased negative feedback sensitivity in coincidence with the reversion of the IS-induced behavioral deficits.