Adrenocorticotropic hormone (ACTH) influences the behavior of both animal and man by a direct action on the nervous system. The N-terminus of the polypeptide hormone is responsible for the behavioral activity. Fragments of that region possess full behavioral and neurophysiological activity but lack the classical endocrine effects of ACTH. Currently, the influence of ACTH-like neuropeptides on brain neuronal activity is best formulated as neurohormonal or neuromodulatory. When ACTH acts as a neurohormone, it reaches its target in the brain via the liquor or blood circulation. An example of such a mode of action is the trophic influence of the peptide on nervous tissue. This influence is evidenced by an enhanced protein synthesis and cell repair. The neuromodulatory action of the peptide involves its release in the vicinity of the synaptic cleft, and the modulation of synaptic efficacy.
Zwiers, H., Jolles, J., Aloyo, V. J., Oestreicher, A. B., & Gispen, W. H. (1982). Acth and synaptic membrane phosphorylation in rat brain. Progress in Brain Research, 56, 405-417. https://doi.org/10.1016/S0079-6123(08)63787-5