Memory as a state dependent phenomenon: role of ACTH and epinephrine

Rats received an ip injection of saline, epinephrine HCl (5.0 micrograms/kg), or ACTH1--24(0.2 microgram/kg) immediately after training in a step-down inhibitory avoidance task, and an ip injection of saline, or epinephrine (0.5, 1.0, 2.0, 3.0, 5.0, or 10.0 mu/kg), or ACTH (0.02, 0.04 0.08, 0.12, 0.2, or 0.4 microgram/kg) 6 min prior to a test session of the same task 24 hr after training. Retention was excellent in the groups treated with saline after training, and poor in those treated with ACTH or epinephrine after training and tested under saline. The amnestic effect of the drugs was counteracted by their administration prior to testing, and there was a dose-response curve for this effect: partial recovery from amnesia was obtained with 20 or 40% of the amnestic dose and full recovery was obtained with 60 to 100% of that dose when the same drug was given after training and prior to testing; if the drugs given after training and prior to testing were not the same, full recovery was obtained only with twice the amnestic dose of the latter. These findings are consistent with the hypothesis that learning depends on the relation between the endogenous levels of these two hormones in the post-training period and during testing. The animals seem capable of discriminating between the two drugs only partially.