REVERSAL OF LEARNED HELPLESSNESS BY MORPHINE IN RATS - INVOLVEMENT OFA DOPAMINE MEDIATION

The aim of this study was to examine the role of dopamine neurotransmi ssion in the effects of morphine in the learned helplessness paradigm in rats, a generally recognized model of depression. In this model, ra ts first exposed to inescapable shocks (stressed rats) exhibited an es cape deficit in a subsequent shuttle-box test performed 48 h later for 3 consecutive days. The numbers of escape failures and intertrial cro ssings (motor activity during each intertrial interval) were recorded. Morphine was injected twice daily for 5 days (6 mg/kg/day, SC), and h aloperidol, a preferential D-2-dopamine receptor antagonist, was injec ted IP 15 min before each shuttle-box session. At the highest dose tes ted (150 mu g/kg) haloperidol mimicked the behavioral deficit produced by inescapable shocks. A 37.5 mu g/kg dose of haloperidol, which was ineffective by itself, reversed the morphine-induced improvement of es cape behavior in previously stressed rats and the morphine-induced inc rease in intertrial activity in both stressed and nonstressed animals. These results support roles (a) for a dysregulation of dopaminergic n euronal activity in the expression of escape deficit subsequent to an inescapable aversive situation, and (b) for a dopaminergic mediation i n the effects of morphine in the learned helplessness paradigm. (C) 19 98 Elsevier Science Inc.