THE EFFECTS OF CCK-4 ON DOPAMINE D-1 AGONIST-INDUCED GROOMING ARE BLOCKED BY A CCKA RECEPTOR ANTAGONIST - EVIDENCE FOR A NOVEL CCK RECEPTORSUBTYPE

The neuropeptide cholecystokinin (CCK) has been shown to interact with dopamine in various ways, including attenuation of dopamine D-1 recep tor-mediated vacuous chewing and grooming. While we have demonstrated a clear role for the CCKA receptor in the attenuation of dopamine D-1 agonist-induced vacuous chewing, studies of grooming yielded anomolous results. We examined the effects of selective CCK receptor antagonist s 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-Daw ley rats resulted in a significant increase in grooming which was redu ced to control levels by CCK-4 (20 mg/kg i.p.). Pretreatment with eith er the CCKA receptor antagonist devazepide or the CCKB receptor antago nist L-365,260 significantly attenuated this effect over a range of do ses (20, 100, 500 mu g/kg i.p.). The suppression of dopamine D-1 agoni st-induced grooming by CCK-4 does not appear to reflect a non-specific effect of anxiogenesis, as it was unaffected by the anxiolytic diazep am. The CCK receptor antagonists alone were without behavioural effect . Taken together with previous studies in models of anxiety and analge sia, our findings lend further support to the hypothesis that CCK-4 ma y act at a novel receptor subtype. (C) 1998 Elsevier Science Ltd. All rights reserved.