CCK A, but not CCK B, agonists suppress the hyperlocomotion induced by endogenous enkephalins, protected from enzymatic degradation by systemic RB 101

Abstract

Interactions between CCKergic and enkephalinergic systems were studied in mice using behavioral responses measured in Animex. The hyperlocomotion induced by 5 mg/kg of RB 101, a mixed inhibitor of enkephalin-degrading enzymes able to cross the blood-brain barrier, was previously shown to be mediated by δ-opioid receptor stimulation. The IP administration of a CCK A agonist, Boc-Tyr-Lys-(CONH- o-tolyl)-Asp-Phe- NH 2 (0.1, 1, 10 μg/ kg), suppressed the hyperlocomotion produced by IV injection of 5 mg/kg of RB 101. The effect of the CCK A agonist was suppressed by a selective CCK A antagonist, devazepide, injected IP at doses of 20 and 200 μg/kg and was potentiated by the selective δ-opioid antagonist naltrindole at the doses of 0.03 mg/kg. IP injection of the selective CCK B agonist BC 264 (0.1–1 mg/kg) did not modify the RB 101-induced hyperlocomotor effect. These results reinforce the observed physiological antagonism between the endogenous CCK and opioid systems but are at variance with the responses measured in stressful conditions. It is concluded that CCK A, but not CCK B, receptor activation counteracts the opioid-related hyperlocomotion.