CCKA, but not CCKB, agonists suppress the hyperlocomotion induced by endogenous enkephalins, protected from enzymatic degradation by systemic RB 101.
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 delta-opioid receptor stimulation. The IP administration of a CCKA agonist, Boc-Tyr-Lys-(CONH-o-tolyl)-Asp-Phe-NH2 (0.1, 1, 10 micrograms/kg), suppressed the hyperlocomotion produced by IV injection of 5 mg/kg of RB 101. The effect of the CCKA agonist was suppressed by a selective CCKA antagonist, devazepide, injected IP at doses of 20 and 200 micrograms/kg and was potentiated by the selective delta-opioid antagonist naltrindole at the doses of 0.03 mg/kg. IP injection of the selective CCKB 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 CCKA, but not CCKB, receptor activation counteracts the opioid-related hyperlocomotion.
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Unité de Pharmacochimie Moléculaire et Structurale, U266 INSERM-URA D1500 CNRS, Université René Descartes-UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
Corringer
P J
PJ
Roques
B P
BP
D000595:Amino Acid Sequence; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000819:agonists* / Q000031:analogs & derivatives / Q000494:pharmacology; D020109:Devazepide; D004220:Disulfides / Q000494:pharmacology*; D004745:Enkephalins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000037:antagonists & inhibitors
C084553:BC 264; D001570:Benzodiazepinones; D004220:Disulfides; D004745:Enkephalins; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; C074024:RB 101; D010649:Phenylalanine; D009271:Naltrexone; D002766:Cholecystokinin; C055382:naltrindole; D020109:Devazepide