ACTH Peptide Modulation of the Developing Mammalian Neuromuscular System Seen through Three Different Perspectives a

The developing neuromuscular system of neonatal rats has been shown to be differentially sensitive to ACTH neuropeptides. Neuromodulation appears to be dependent upon the specific ACTH fragment and the dosage administered.' Both ACTH 4-10 and the trisubstituted analogue ACTH 4-9 (Org 2766) have potent behavioral effects in adult animals, the ACTH 4-9 analogue being 1000 times as potent as ACTH 4-10.' In neonatal rats, using the same dosage (0.1 pg/kg) for these two peptides, only ACTH 4-9 effectively elevated motor activity following cold stress.' However, electrophysiological investigation of the developing neuromuscular system showed this dosage (0.1 pg/kg) of ACTH 4-10, a dosage that was ineffective in behavioral studies, to be highly effective in increasing muscle contraction amplitude, decreasing half-relaxation time and delaying fatigue.' In the present study, we have attempted to correlate the effects of both these peptides on electrophysiological responses, the development of motor activity, and morphological changes in the peripheral neuromuscular system.