Prevention of “learned helplessness” in the rat by hydroxyzine



The effects of hydroxyzine (8, 16, and 32 mg/kg i.p.), administered either 30 min before exposing rats to a series of inescapable shocks (preventive treatment) or during the subsequent acquisition of a shuttle box avoidance response (curative treatment), wereinvestigated. In these conditions untreated rats, previously exposed to inescapable shocks (“stress” ), show a marked increase in escape failures in the shuttle box when compared with nonshocked control animals (“ learned helplessness” ). Control experiments examined the effects of hydroxyzine on memory (passive avoidance test) and on electric shock sensitivity. Diazepam (2 mg/kg i.p.) was used as a reference compound. Hydroxyzine, when administered before “ stress,” clearly decreased at 8 and 32 mg/kg the number of escape failures observed but was without effect when administered after “stress” during the subsequent shuttle box avoidance learning. Similar results were observed with diazepam. Unlike diazepam, hydroxyzine at 32 mg/kg−1 induced no amnesia in the passive avoidance test, whereas clear amnesia was observed with diazepam. Neither compound altered the rats' sensitivity to shock. These results suggest that hydroxyzine decreases the effects of “ stress” and that these effects cannot be attributed either to impaired memory for the aversive stimulation or to diminished shock sensitivity.