The effects of CCK-4 on dopamine D1 agonist-induced grooming are blocked by a CCK(A) receptor antagonist: evidence for a novel CCK receptor subtype?
The neuropeptide cholecystokinin (CCK) has been shown to interact with dopamine in various ways, including attenuation of dopamine D1 receptor-mediated vacuous chewing and grooming. While we have demonstrated a clear role for the CCK(A) receptor in the attenuation of dopamine D1 agonist-induced vacuous chewing, studies of grooming yielded anomalous results. We examined the effects of selective CCK receptor antagonists on the attenuation of SKF 38393-induced grooming by the CCKB agonist CCK-4. Administration of SKF 38393 (5 mg/kg s.c.) to male Sprague-Dawley rats resulted in a significant increase in grooming which was reduced to control levels by CCK-4 (20 mg/kg i.p.). Pretreatment with either the CCKA receptor antagonist devazepide or the CCK(B) receptor antagonist L-365,260 significantly attenuated this effect over a range of doses (20, 100, 500 microg/kg i.p.). The suppression of dopamine D1 agonist-induced grooming by CCK-4 does not appear to reflect a non-specific effect of anxiogenesis, as it was unaffected by the anxiolytic diazepam. The CCK receptor antagonists alone were without behavioural effect. Taken together with previous studies in models of anxiety and analgesia, our findings lend further support to the hypothesis that CCK-4 may act at a novel receptor subtype.
van Kampen
J
J
Neurodegenerative Disorders Centre, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Stoessl
A J
AJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide; D003975:Diazepam / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D010671:Phenylurea Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D017447:Receptors, Dopamine D1 / Q000819:agonists*
D001570:Benzodiazepinones; D018491:Dopamine Agonists; D018757:GABA Modulators; D006727:Hormone Antagonists; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D017447:Receptors, Dopamine D1; C058121:L 365260; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D002766:Cholecystokinin; D020109:Devazepide; D003975:Diazepam