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, s.c.), and haloperidol, a preferential D2-dopamine receptor antagonist, was injected i.p. 15 min before each shuttle-box session. At the highest dose tested (150 microg/kg) haloperidol mimicked the behavioral deficit produced by inescapable shocks. A 37.5 microg/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.
Besson
A
A
Laboratoire de Pharmacologie, Faculté de Pharmacie, Equipe NPPUA, Clermont-Ferrand, France.
Privat
A M
AM
Eschalier
A
A
Fialip
J
J
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D004597:Electroshock; D004924:Escape Reaction / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006380:Helplessness, Learned; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018492:Dopamine Antagonists; D009294:Narcotics; D009020:Morphine; D006220:Haloperidol; D004298:Dopamine