Cholecystokinin increases extracellular dopamine overflow in the anterior nucleus accumbens via CCK(B) receptors in the VTA assessed by in vivo voltammetry.
Differential pulse voltammetry was used to investigate the extracellular dopamine (DA) and DOPAC signal in the anterior part of nucleus accumbens (N.acc.) after microinjection of cholecystokinin (CCK) derivatives into the ventral tegmental area (VTA). Both the mixed CCK(A)/CCK(B) receptor agonist CCK-8s and the selective CCK(B) receptor agonist CCK-4 caused a dose-dependent increase in the DA signal after doses of 10 ng and 100 ng while CCK-8s had no effect on the DOPAC signal. The CCK(A) receptor antagonist L 364,718 (25 microg/kg i.p.) as well as the CCK(B) receptor antagonist L 365,260 (25 microg/kg i.p.) were administered prior to microinjection of 100 ng CCK-8s and L 365,260, but not L 364,718, completely inhibiting the DA increase produced by CCK-8s. Analysis of the tissue levels of DA and its main metabolites in the anterior part of N.acc. revealed no changes after CCK-8s microapplication into VTA. The presented data indicate a CCK(B) receptor-mediated increase in extracellular DA in the anterior N.acc. after microapplication of CCK derivatives into the VTA.
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Institute of Pharmacology and Toxicology, Medical Faculty (Charité), Humboldt-University at Berlin, Germany.
Schäfer
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Marsden
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Fink
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Morgenstern
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D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000737:chemistry / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D010671:Phenylurea Compounds; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013758:Tetragastrin / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000378:metabolism*
C090019:8-sulfocholecystokinin octapeptide; D001570:Benzodiazepinones; D006727:Hormone Antagonists; D008996:Monoamine Oxidase Inhibitors; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C058121:L 365260; D002766:Cholecystokinin; D010293:Pargyline; D020109:Devazepide; D012844:Sincalide; D004298:Dopamine