Inhibitory Effect of ACTH and Related Peptides on Extinction of Conditioned Avoidance Behavior in Rats

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Abstract
Summary ACTH, administered during extinction, delays extinction of an avoidance response in rats. To study structure activity relationships, the rate of extinction of an avoidance response performed in a shuttle-box and a pole jumping situation, was investigated in rats treated during the extinction period with ACTH (A3 peptide), synthetic ACTH β 1-24, β-MSH, α-MSH, ACTH 1-10, ACTH 5-10, and ACTH 11-24, administered as long acting zinc phosphate preparations. Zinc phosphate complex and protamine zinc insulin (PZI) were used as placebo control substances. It appeared that ACTH and related peptides significantly delayed the rate of extinction of the avoidance response. Full activity was obtained with ACTH 1-10 peptide while ACTH 5-10 was less active. ACTH 11-24 and PZI were without effect. These results were interpreted to indicate that the active part of ACTH in this respect is located in the N-terminal part of the molecule, presumably in the first 10 amino acids.