In these experiments, post-trial injections of adrenocorticotrophic hormone (ACTH) produced both enhancement and impairment of memory processes. Animals were trained in a one-trial inhibitory (passive) avoidance task and were tested for retention 24 hr later. In the first experiment, animals were trained in the avoidance task using a weak footshock. Immediate post-trial ACTH injections at two doses (0.03 or 0.3 IU/animal) enhanced later retention performance as compared to saline-injected control animals. If animals received a, higher ACTH dose (3.0 IU/rat), the treatment produced retrograde amnesia; i.e., there was an inverted-U dose-response curve for the effects of ACTH on memory. Both enhancement and impairment of memory processes were time-dependent; the effect on memory decreased as the time after training increased. The findings of a second experiment indicated that retention performance of control animals varied with time of day. Control animals trained and tested in the morning (9-10:00 AM) show retention performance significantly poorer than that of animals trained and tested in the afternoon (1-2:00 PM). Post-trial injections of ACTH enhanced later retention only in the afternoon conditions. A third experiment examined the interactions between the footshock parameters used in training and the effect, on memory, of ACTH. A single post-trial dose of ACTH (either 3 or 6 IU/rat) enhanced later retention of training with weak footshock and impaired later retention of training with a more intense footshock. These findings support the general view that ACTH may modulate memory storage processing of recent information. In addition, these results suggest the possibility that other post-trial treatments which facilitate or impair memory processes may act via hormonal mechanisms.
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