Antistereotypic effects of cholecystokinin octapeptide (CCK-8), ceruletide and related peptides on apomorphine-induced gnawing in sensitized mice

Cholecystokinin octapeptide (CCK-8), ceruletide (caerulein, CER) and 7 analogues of ceruletide, were studied for antagonism of stereotyped gnawing and cage climbing, induced by apomorphine in mice that were sensitized by either administration of scopolamine (1 mg/kg, s.c., 15 min before) or teflutixol (5 mg/kg, i.p., 4 days before). Three neuroleptics (haloperidol, trifluoperazine and teflutixol) served as reference drugs. All peptides reduced or abolished the fully developed gnawing activity and were (on a molar basis) often more potent than the reference drugs. In contrast to the neuroleptics, the peptides did not antagonize the climbing activity. In mice pretreated with scopolamine, the peptides were more potent than in mice pretreated with teflutixol. With the neuroleptics, the influence of the sensitizing pretreatments was converse, and this applied also to the anticlimbing effect. The relationships between peptide structure and antistereotypic effect were different from those found previously in a study on the antagonism of gnawing induced by methylphenidate. Conclusions: CCK-like peptides are able to antagonize stereotyped behaviour caused by direct and indirect dopaminergic agonists; the mechanism of action of the peptides differs from that of the reference neuroleptics.