ABSTRACT
Mirsky and colleagues suggested in 1953 that adrenocorticotropic hormone (ACTH) could affect behavior when they observed that daily administration of this hypophyseal hormone to rats delayed extinction of conditioned avoidance behavior (Mirsky, Miller, & Stein, 1953). ACTH(1–39) is a trophic hormone that governs the activity of the adrenal cortex. Each damaging stimulus (“stress”) is followed by an increased hypophyseal secretion of ACTH, leading to increased activity of the adrenal cortex. The latter, in turn, produces stress hormones, such as cortisol, that are required for the defense of the organism against deleterious stimuli (stress). The effect of ACTH observed in Mirsky’s experiment was considered, at that time, to be an effect of the hormones produced by the adrenal cortex. One of Mirsky’s colleagues, Miller, and I performed an experiment in 1957 (unpublished observations) in which we studied the effect of prednisolone, a synthetic compound with corticosteroid activity, on the extinction of avoidance behavior. We expected an effect identical to that of ACTH. We were surprised to find that daily administration of this hormone accelerated the extinction of avoidance behavior. The implication was that the effect of ACTH had not been caused by its “classical” effect on the adrenal cortex. We were probably dealing with a hitherto unknown effect of ACTH.
