Reversal of Learned Helplessness by Morphine in Rats ☆: Involvement of a Dopamine Mediation A. Besson*, A.M. Privat*, A. Eschalier†, J. Fialip*,
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 D2-dopamine receptor antagonist, was injected IP 15 min before each shuttle-box session. At the highest dose tested (150 μg/kg) haloperidol mimicked the behavioral deficit produced by inescapable shocks. A 37.5 μg/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. Keywords Learned helplessness; Morphine; Haloperidol; Dopamine; Rats ☆ The procedure used to kill the animals in this study is not allowed in UK or USA. Prof. J. Fialip, Laboratoire de Pharmacologie, Faculté de Pharmacie, 28, Place Henri Dunant, BP38, 63001 Clermont-Ferrand cedex 1, France
Source: Reversal of Learned Helplessness by Morphine in Rats: Involvement of a Dopamine Mediation