Comparative effects of the ACTH 4–9 analogue (ORG 2766), ACTH 4–10 and [ d-Phe 7] ACTH 4ndash;10 on medial septal self-stimulation behaviour in rats

Abstract

Experiments were performed to examine the effects of various analogues of ACTH on electrical self-stimulation behaviour elicited from the medial septal area using an ascending or descending sequence of stimulus intensities within a session. When an ascending sequence of threshold multiples was used ACTH 4–10 and the ACTH 4–9 analogue (ORG 2766) enhanced lever pressing for low intensity stimulation but attenuated self-stimulation at greater current intensities. The analogue ORG 2766 appeared to be a thousand times more potent than ACTH 4–10; [ d-Phe 7] ACTH 4–10 inhibited the response rate at threshold level but was inactive at greater current intensities. The same effect was found following administration of ORG 2766 in a dose which was 20 times greater (1 μg/rat) than that used in the first experiments. Lever pressing was not affected by treatment with ACTH 4–10 or ORG 2766 when a descending sequence of stimulus intensities was used within a session. Thus, ACTH-related peptides may affect motivational processes involved in self-stimulation rather than the reward of the stimulation per se. It is suggested that although ORG 2766 mimicked the action of ACTH 4–10 this synthetic peptide may have additional behavioural properties.