Peripheral stimulation of CCK-B receptors by BC264 induces a hyperexploration, dependent on the delta opioid system in the nucleus accumbens of rat.
This study analyses the influence of the CCKergic system on the enkephalinergic system in the exploratory behavior of rats, using both behavioral and biochemical approaches. The results show that the increase of the spontaneous alternation behavior induced by the selective CCKB agonist, BC264 (3 microg/kg) was not suppressed by the opioid antagonists, naloxone (100 microg/kg), or naltrindole (300 microg/kg). In contrast, BC264 injected at the same dose induced a hyperlocomotor activity measured in the open-field test, which was antagonized by the selective delta opioid antagonist, naltrindole. BC264 (3 microg/kg) significantly increased the extracellular levels of Met-LI in the anterior part of the nucleus accumbens. Furthermore, local injection of naltrindole (0.25 microg/0.5 microl) in the anterior nucleus accumbens completely suppressed the hyperlocomotion induced by BC264. The behavioral effects induced by BC264 cannot be explained by its interaction with gastrinic receptors mediating gastric acid release, since BC264 produced a long-lasting increase of gastric acid output from conscious gastric fistula rats only at doses 100 times higher than those inducing behavioral modifications. The hyperlocomotion obtained after stimulation by BC264 of probably peripheral CCKB receptors, indicates that this receptor type could participate in the transmission of information between the peripheral system and some regions of the CNS involved in motivations and emotions.
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Département de Pharmacochimie Moléculaire et Structurale, INSERM U266-UMR 8600 CNRS, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
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D000818:Animals; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*
C084553:BC 264; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D017465:Receptors, Opioid, delta; D009271:Naltrexone; D002766:Cholecystokinin; C055382:naltrindole