Effects of corticotrophin (ACTH) on recovery of sensorimotor function in the rat: structure-activity study

The recovery of sensorimotor function in rats was studied using a foot-flick response test after crushing the sciatic nerve. Every other day, the animals received a subcutaneous injection of ACTH1-24 or vehicle, immediately after the 'foot-flick' test. Rats treated with ACTH1-24 showed a faster recovery of sensorimotor function as compared to vehicle-treated rats. This beneficial effect was dose-dependent. In contrast, no effect on toe-spreading could be detected. To investigate what part of the peptide molecule would contain the active site and to exclude steroid mediation, smaller sequences of ACTH1-24 devoid of corticotrophic activity were tested. Treatment with ACTH1-16NH2, ACTH4-10 or [Met(O2)4,D-Lys8,Phe9]ACTH4-9 (Org. 2766) mimicked the effect of ACTH1-24, whereas treatment with ACTH11-24 did not effect the return of sensorimotor function. The stimulatory effects of corticotrophin1-24 and congeners on recovery of sensorimotor function are discussed in terms of a direct effect of these peptides on nervous tissue, probably through enhanced brain and spinal cord protein synthesis.