Fragments of ACTH affect electrophysiological signs of controlled stimulus processing in humans

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Abstract
It has been proposed that the systemic administration of the 4–10 fragment of ACTH in humans affects primarily attention. In the present study, influences of ACTH 4-10 on event-related potential (ERP) indicators of attention were evaluated in healthy men. The influences were compared with those of an analog of the ACTH 4-9 sequence (HOE 427) which was expected to have an increased potency. Following an adaptation session, each of 20 healthy men was tested on four occasions in a double-blind study designed according to a latin-square. On each occasion, subjects received (iv) one of the following treatments: placebo, ACTH 4-10 (1 mg), HOE 427 (60 μg) and HOE 427 (200 μg). Treatments were administered 40 min prior to recordings of ERPs. ERPs were recorded while the subjects performed on a dichotic listening task paradigm. The various tone pips presented in this task elicit ERPs providing measures of controlled stimulus processing (Nd reflecting selectivity of attention, and P3) and automatic processing of stimulus deviance (mismatch negativity). ACTH 4-10 as well as 200 μg HOE 427 reduced Nd and also P3 amplitudes following attended stimuli. Smaller (non-significant) changes in the same direction were observed following 60 μg HOE 427. The results suggest an impairing influence of ACTH 4-10 and of HOE 427 on signs of controlled stimulus processing, particularly on the Nd. The analog appeared to be more potent than the endogenous 4–10 fragment.