Retention impairment by posttraining epinephrine: role of state dependency and of endogenous opioid mechanisms.

Mice were trained in a step-through inhibitory avoidance task with a 0.6-mA, 60-Hz, 2-s footshock and were tested for retention 3 or 6 hr later. Posttraining intraperitoneal administration of a high dose (25.0 micrograms per mouse) of epinephrine (Epi) impaired retention; this effect was counteracted by another injection of the same dose of Epi given before retention testing either 3 or 6 hr after training. When administered before the 6-hr test but not the 3-hr test, however, Epi enhanced retention (i.e., above that of controls). The retention enhancement, but not the reversal of impairing effects of posttraining Epi, was antagonized by naltrexone (20.0 micrograms per mouse). Naltrexone, when administered alone, had no effect on retention when given before testing. However, posttraining administration of naltrexone produced an enhancement of retention detectable 6 but not 3 hr after training. Furthermore, posttraining naltrexone also blocked the impairing effect of posttraining Epi otherwise seen 6 hr after training. These results suggest that the impairment of retention caused by posttraining Epi is attributable to the induction of state dependency based on an Epi state. When the animals are tested 3 hr after training, this effect appears alone. But, when tested 6 hr after training, the Epi effect appears together with an opioid, presumably beta-endorphin-mediated, state dependency.