Similar potencies of CCK-8 and its analogue BOC(Nle28;Nle31)CCK27-33 on the self-stimulation behaviour both are antagonized by a newly synthesized cyclic CCK analogue.
Neurons with co-localized cholecystokinin (CCK) and dopamine (DA) are present predominantly in the ventral tegmental area (VTA) and project mainly to the caudal part of the medial nucleus accumbens. The activity of this dopaminergic system can be evaluated by means of the intracranial self-stimulation behaviour (ICSS) on male Wistar rats having chronic electrodes implanted into the medial forebrain bundle in the postero-lateral area of the hypothalamus. The direct injection of the CCK analogue BOC(Nle28;Nle31)CCK27-33 (BDNL-CCK7) into a lateral ventricle decreased the electrical self-stimulation of the medial forebrain bundle. Nevertheless, this decrease in self-stimulation was steeper (immediately after the injection vs a delay of +/- 5-10 min.) than the CCK8-induced ICSS depletion. The intracerebroventricular (ICV) injection of 150 pmol and 1000 pmol BC-197 (BOC-D.Asp-Tyr(SO3H)-Nle-D.Lys-Trp-Nle-Asp-Phe-NH2) was ineffective to modify the self-stimulation behaviour when administered alone while a 150 pmol BC-197 dosage was able to antagonize the decreasing effect of 150 pmol CCK-8 on ICSS. Nevertheless, a dosage 6 times as important, i.e. 1000 pmol BC-197, was needed to antagonize the depression induced by 150 pmol BDNL-CCK7 on ICSS behaviour. These results support the equipotence of BDNL-CCK7 to CCK-8 in decreasing the self-stimulation behaviour after their direct administration into the lateral ventricle. They further give evidence of the relevance of BC-197 in antagonizing the respective effects of both compounds on the ICSS.
Heidbreder
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Laboratoire de Psychobiologie, Université de Louvain, Louvain-La-Neuve, Belgium.
Roques
B P
BP
De Witte
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P
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects*; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects; D012653:Self Stimulation / Q000187:drug effects*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology*
D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; C060186:BC 197; D002766:Cholecystokinin; C047716:cholecystokinin (27-33), tert-butyloxycarbonyl-Nle(28,31)-; D012844:Sincalide