Effects of Cholecystokinin Octapeptides and Their Fragments on the Acquisition and Extinction of Active Avoidance Behavior of Rats

Abstract

The effects of peripheral (subcutaneous or intraperitoneal) and central (intracerebroventricular or intracerebral) administration of cholecystokinin octapeptides (CCK-8; sulphated: CCK-8-SE; non-sulphated; CCK-8-NS) and their fragments have been investigated on the acquisition and extinction of fear-motivated active avoidance behaviour of rats CCK-8 and also their COOH-terminal tetrapeptide inhibited acquisition and facilitated extinction of active avoidance behaviour in a dose-dependent manner. These effects of CCK-8 were partially inhibited by CCK antagonists, proglumide or benzotript. Effects of peripheral administered CCK-8-SE or CCK-8-NS have also been studied on these behavioural reactions following bilateral electrolytic and neurotoxic (induced by 6-hydroxydopamine; 6-OHDA) lesions in the ventral tegmental area (VTA), nucleus accumbens septi (NAS) or nucleus amygdalae centralis (NAC). Subcutaneous treatment with CCK-8-SE or CCK-8-NS dose-dependently delayed the extinction of active avoidance behaviour following electrolytic lesions of NAS. Extinction of active avoidance behaviour was facilitated in rats with electrolytic lesions of NAC. No difference was found between sham-operated and VTA-lesioned animals following CCK-8-SE or CCK-8-NS treatment. Only a slight difference was shown between effect of CCK-8-SE and CCK-8-NS in groups with 6-OHDA lesions of NAS or NAC.