Effects of systemic and intracerebral administration of two opposite acting ACTH-related peptides on extinction of conditioned avoidance behavior.

The effects of the decapeptide ACTH-(1–10) and [D-phe7]-ACTH-(1–10) were tested on the rate of extinction of a pole-jumping avoidance response in rats. ACTH-(1–10) in doses of 20, 50, and 100 µg inhibited extinction of the avoidance response 4 h following subcutaneous administration. [D-phe7]-ACTH-(1–10) in doses of 20, 50, and 100 µg facilitated extinction 4 h after injection. Intracerebral implantation of approximately 10 µg of these ACTH-analogues in the freely moving rat had similar effects on extinction of avoidance response when implanted into the region of the rostral mesencephalon and the caudal diencephalon, at the posterior thalamic level, or in the cerebrospinal fluid. Ineffective sites were the nucleus ventralis thalami, the nucleus anterior medialis thalami, the nucleus reuniens, the globus pallidus, the nucleus accumbens, the fornix, and the hippocampus. The results support the hypothesis that the site of action of ACTH and of ACTH-analogues on extinction of an avoidance response is localized in the central nervous system.