Reversal of learned helplessness by morphine in rats: Involvement of a dopamine mediation

The aim of this study was to examine the role of dopamine neurotransmission in the effects of morphine in the learned helplessness paradigm in rats, a generally recognized model of depression. In this model, rats first exposed to inescapable shocks (stressed rats) exhibited an escape deficit in a subsequent shuttle-box test performed 48 h later for 3 consecutive days. The numbers of escape failures and intertrial crossings (motor activity during each intertrial interval) were recorded. Morphine was injected twice daily for 5 days (6 mg/kg/day, SC), and haloperidol, a preferential D-2-dopamine receptor antagonist, was injected IP 15 min before each shuttle-box session. At the highest dose tested (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 escape behavior in previously stressed rats and the morphine-induced increase in intertrial activity in both stressed and nonstressed animals. These results support roles (a) for a dysregulation of dopaminergic neuronal activity in the expression of escape deficit subsequent to an inescapable aversive situation, and (b) for a dopaminergic mediation in the effects of morphine in the learned helplessness paradigm. (C) 1998 Elsevier Science Inc.