Effect of ACTH, epinephrine, beta-endorphin, naloxone, and of the combination of naloxone or beta-endorphin with ACTH or epinephrine on memory consolidation.

The effect on retention of the post-training intraperitoneal administration of ACTH1-24 (0.2 or 2.0 micrograms/kg), epinephrine HCl (5.0 or 50.0 micrograms/kg), human beta-endorphin (0.1 or 1.0 microgram/kg), naloxone (0.4 mg/kg), and of the combination of naloxone or beta-endorphin with ACTH or epinephrine was studied in two different but closely related step-down inhibitory avoidance tasks in rats: task 1 (5 cm high 25 X 25 cm platform; 0.5 mA continuous footshock) and task 2 (7 X 25 cm platform, 0.3 mA discontinuous footshock). In task 1, saline control animals showed good retention in a test session carried out 24 hr later; beta-endorphin, ACTH and epinephrine caused amnesia; beta-endorphin potentiated the amnesic effect of ACTH and epinephrine; and naloxone caused memory facilitation and reversed the amnesic effect of ACTH and epinephrine. In task 2, control animals showed poor retention; beta-endorphin caused amnesia at the dose of 0.1 but not 1.0 microgram/kg; the other three drugs caused memory facilitation; naloxone potentiated the facilitatory effect of ACTH and epinephrine; and beta-endorphin reversed it and transformed it into a deep amnesia. These findings suggest that an opioid-mediated amnesic mechanism modulates the effect of ACTH and epinephrine on memory consolidation, either by dampening that effect when training parameters tend to make it facilitatory, or by enhancing it when training conditions tend to make it amnesic. On the basis of these and previous data it seems likely that the amnesic effect of ACTH and epinephrine could be mediated by endogenous beta-endorphin release.