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.