The Influences of ACTH 4–9 Analog upon Avoidance Learning in Normal and Brain Damaged Rats

Abstract

The potential benefits of exogenous administration of the adrenocorticotropic hormone (ACTH) and some of its fragments following nervous system damage has been examined sporadically over the past 40 years. Early research (e.g., 1) reported that administration of ACTH resulted in limited functional recovery in some animals after spinal cord damage, and these beneficial effects seemed to be associated with administration shortly after the injury. Strand and Kung (2) found that ACTH accelerated the rate of nerve regeneration following nerve crush in adrenalectomized animals and concluded that ACTH stimulated an increase in protein and RNA synthesis in spinal motor neurons. Strand and Smith (3) have hypothesized that this enhanced protein synthesis results in increased synthesis and/or delivery of neurotransmitters or neurotrophic substances to sprouting axons. Similarly, it has been reported (4,5) that ACTH 1–39 facilitates functional reorganization of motor units and hastens functional recovery following either peroneal or sciatic nerve crush. Bijlsma and colleagues (6) concluded that the 4–10 amino acid sequence of ACTH was responsible for the hormone’s beneficial action on peripheral nerve regeneration and accelerated recovery of a foot-flick response. In a test of this hypothesis, these researchers repeated their earlier methodology, again using animals with crushed sciatic nerves, and found that treatment with ACTH 4–10 resulted in a striking increase in the number of myelinated axons throughout the regeneration process. Treatment with the 11–24 fragment of ACTH produced no beneficial effects. This observation has been replicated recently (7) with both fiber density and regeneration rate facilitated by ACTH 4–10 following sciatic nerve crush. Since the 4–10 (and 4–9) sequence of the hormone fails to exert an endocrine effect upon the adrenal cortex (8), it has been concluded that the facilitated nerve regeneration is independent of the corticotropic (or peripheral) influences of the hormone (6).