In rats, the behavioral profile of CCK-8 related peptides resembles that of antipsychotic agents

Abstract

The action of some CCK-8 related peptides, desulphated CCK-8 (CCK-DS), the sulphated form of CCK-8 (CCK-8-S) and ceruletide was explored in a number of test procedures with rats, in which antipsychotic agents are active. Following injection into the nucleus accembens, all three peptides antagonized the hypolocomotion induced by low doses of apomorphine (10 ng). Ceruletide appeared to be the most potent in this respect (ED 50: approximately 5 pg). The increased locomotion observed following injection of relatively high doses of apomorphine (10 μg) into the nucleus accumbens was antagonized by local pretreatment with CCK-8-S, but not with CCK-8-DS or ceruletide. None of these CCK-8 related peptides affected the stereotyped sniffing response elicited by treatment with apomorphine or amphetamine (10 μg) given into the nucleus caudatus. Passive avoidance behavior was facilitated following subcuttaneous administration of 10 μg of CCK-8-related peptides 1 h before the retention test. The same peptides given into the nucleus accumbens (0.3 pg) however attenuated passive avoidance behavior. Intraventricular injection with CCK-8-DS and CCK-8-S induced a positive effect in various ‘grip tests’. Given subcutaneously, the CCK-8-related peptides decreased the rate of ambulation and rearing especially in the middle of the open field. These results indicate that CCK-8 related peptides, especially CCK-8-DS and ceruletide, exhibit behavioral effects that are similar to those observed following treatment with γ-type endorphins and that resemble the effects of antipsychotic agents. Very low doses of CCK-8 related peptides exert behavioral effects following injection into the nucleus accumbens, indicating that this brain area is extremely sensitive to the action of these peptides. It is postulated that certain peptides which are either present in neurons (like CCK-8-related peptides) or generated by brain endorphin systems (like γ-type endorphins) control the activity of specific neurons of the mesolimbic dopaminergic pathways. This may be of relevance for the purported antipsychotic action of these peptides.