Mutant mice lacking the cholecystokinin2 receptor show a dopamine-dependent hyperactivity and a behavioral sensitization to morphine.
Cholecystokinin2 (CCK2) receptor-deficient mice were used to analyze the in vivo function of CCK2 receptor and especially the incidence of this gene invalidation on enkephalinergic and dopaminergic systems. Hyperlocomotor activity of CCK2 receptor-deficient mice was suppressed by a selective D2 antagonist but not by a D1 antagonist. Injection of amphetamine induced a hyperlocomotor activity in both groups of mice while mutant mice were less sensitive to cocaine. Administration of 6 mg/kg of morphine once every 2 days for 5 days significantly (P<0.05) enhanced motor activity the last day compared to the first day, only in CCK2 receptor-deficient mice. These results emphasize the role of CCK2 receptors in counteracting the effects of dopaminergic systems and suggest that CCK2 receptor invalidation could lead to a slight behavioral sensitization.
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Département de Pharmacochimie Moléculaire et Structurale, INSERM U266-CNRS UMR 8600, UFR des Sciences Pharmaceutiques et Biologiques, 4, avenue de l'Observatoire, 75270 Cedex 06, Paris, France. dauge@pharmacie.univ-paris5.fr
Beslot
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Matsui
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Roques
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D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002766:Cholecystokinin / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D006948:Hyperkinesis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
D000701:Analgesics, Opioid; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004745:Enkephalins; D011949:Receptors, Cholecystokinin; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D009020:Morphine; D002766:Cholecystokinin; D004298:Dopamine