Effects of morphine, naloxone and their interaction in the learned-helplessness paradigm in rats.
The aim of this study was to investigate the possible involvement of the mu-opioid system on the learned-helplessness paradigm, an experimental model of depression, in rats. In this test, rats were first exposed to inescapable foot-shocks (IS); 48 h later, they were submitted to a daily shuttle-box session (30 trials) for 3 consecutive days. Avoidance responses, escape failures and animal activity during each intertrial interval were recorded. Twice daily injections of morphine (0.25-8 mg/kg per day, SC), a mu-opioid agonist, reduced the increased escape failures induced by IS, as did tricyclic antidepressants. Significantly higher intertrial activity was observed in rats treated with morphine (2-8 mg/kg per day) compared with their associated control groups. Naloxone (1 and 2 mg/kg, IP), a mu-opioid antagonist, injected 10 min before each shuttle-box session impaired escape behavior in non-stressed rats and worsened the escape deficit induced by IS. Morphine-induced improvement of escape behavior and increase in intertrial activity were clearly reversed by a low inactive dose of naloxone (0.5 mg/kg). These results suggest that mu-opioid receptor mediation is involved in the deleterious effects of uncontrollable stress.
Besson
A
A
Laboratoire de Pharmacologie, Faculte de Pharmacie, Clermont-Ferrand, France.
Privat
A M
AM
Eschalier
A
A
Fialip
J
J
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006380:Helplessness, Learned; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D009270:Naloxone; D009020:Morphine