Analogues of ACTH, Conditioned Avoidance Behaviour and Metabolism of Macromolecules in Brain of Rat

Abstract

There is considerable evidence to indicate that the hormones of the pituitary-adrenal system exert an important influence on active avoidance behaviour (De Wied, 1969; De Wied et al., 1972). Removal of the pituitary gland causes a marked impairment in the performance of rats during learning of a shuttlebox avoidance response (De Wied, 1964). Treatment of hypophysectomized rats with ACTH raises the performance towards that of intact animals. Molecules corresponding to fragments of ACTH (see Table 1) containing the amino acid sequence 4–10 have a similar effect (De Wied, 1969). Since these ACTH-analogues have been found to posses neither endocrine nor peripheral metabolic activities, it is obvious that their behavioural influence is due to an extra-adrenal effect, presumably located in the central nervous system (Van Wimersma Greidanus and De Wied, 1971). The finding (Bohus and De Wied, 1966) that ACTH_1–10 with the D-isomer of phenylalanine in position 7 (see Table 1) has the opposite behavioural effect to ACTH_1–10 7-L-Phe suggests a specific interaction of these peptides with the central nervous system.