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Am J Physiol Regul Integr Comp Physiol 263: R125-R135, 1992;
0363-6119/92 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 263, Issue 1 125-R135, Copyright © 1992 by American Physiological Society

ARTICLES

Behavioral effects of A71623, a highly selective CCK-A agonist tetrapeptide

K. E. Asin, L. Bednarz, A. L. Nikkel, P. A. Gore Jr, W. E. Montana, M. J. Cullen, K. Shiosaki, R. Craig and A. M. Nadzan
Neuroscience Research Division, Abbott Laboratories, Abbott Park, Illinois 60064.

We studied the behavioral effects of a novel cholecystokinin tetrapeptide (CCK-4) analogue, A71623, with full agonist activity and high affinity and selectivity for the CCK-A receptor subtype relative to the CCK-B receptor. In tests for anorectic activity, A71623 was found to suppress 60-min intakes of a liquid diet in both deprived and sated rats, and the effects were blocked by a selective CCK-A antagonist, A70104. Compared with CCK-8, A71623 was found to have improved potency and duration of action; the most potent route of administration was intraperitoneal. A71623 also suppressed the intake of a liquid diet and a 0.2 M sucrose solution in lean and obese Zucker rats. In daily injection studies, the anorectic activity of CCK-8 diminished rapidly, whereas the suppressant effects of A71623 on food intakes and body weight gains persisted throughout the 11-day treatment period. Finally, A71623 reduced the spontaneous locomotor activity of rats at doses above those required to suppress intakes. These studies are the first to describe the behavioral effects of a potent and highly selective CCK-A receptor agonist.


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