Behavioral activity of a short chain ACTH analog.

The behavioral activity of ACTH1-17 analog (beta-Ala1, Lys17) ACTH1-17-4 -amino-n-butilamide (Ala1-Lys17-ACTH1-17) has been studied in the rat. Acquisition of shuttle-box active avoidance behavior was facilitated by Ala1-Lys17-ACTH1-17 administered both subcutaneously (SC) and intracerebroventricularly (ICV), and this effect was suppressed by peripheral administration of haloperidol or naltrexone. Extinction of pole jumping active avoidance behavior was delayed by SC administration of the peptide in a dose-dependent manner. Retention of a step-through passive avoidance behavior was facilitated SC or ICV injection of Ala1-Lys17-ACTH1-17. Adrenalectomy failed to modify the effects of the peptide on the retention of passive avoidance behavior. Furthermore, ICV injection of graded doses of Ala1-Lys17-ACTH1-17 induced excessive grooming, and this effect was totally prevented by intraperitoneal (IP) injection of haloperidol or naltrexone SC administration of Ala1-Lys17-ACTH1-17 induced a slight but significant increase in negative responses in a test for behavioral responsiveness to electrical footshock. This effect was totally prevented by IP injection of naltrexone. It is concluded that Ala-Lys17-ACTH1-17 shares some of the behavioral effects of ACTH4-10 and some ACTH1-24, but it seems to be more potent than the latter peptides. Both dopamine and opioid transmission seem to be involved in the behavioral activity of Ala1-Lys17-ACTH1-17.