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 t he mu-opioid system on the learned-helplessness paradigm, an experimen tal model of depression, in rats. In this test, rats were first expose d to inescapable foot-shocks (IS); 48 h later, they were submitted to a daily shuttle-box session (30 trials) for 3 consecutive days. Avoida nce responses, escape failures and animal activity during each intertr ial 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. Significantl y higher intertrial activity was observed in rats treated with morphin e (2-8mg/kg per day) compared with their associated control groups, Na loxone (1 and 2 mg/kg, IF), a mu-opioid antagonist, injected 10 min be fore 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 wer e clearly reversed by a low inactive dose of naloxone (0.5 mg/kg). The se results suggest that mu-opioid receptor mediation is involved in th e deleterious effects of uncontrollable stress.