title: Morphine place conditioning is differentially affected by CCKA and CCKB receptor antagonists.
abstract: In the present study we have examined the interaction between the selective cholecystokinin (CCK)A and CCKB receptor antagonists, devazepide and L365-260 on morphine conditioned place preference (CPP). Using an unbiased procedure, morphine (1.5 mg/kg) produced a reliable CPP which was observed irrespective of the conditioning compartment type. Pretreatment with devazepide (0.001-0.01 mg/kg s.c.) produced a dose related attenuation of this response. At higher doses (0.1-1 mg/kg) this antagonism became variable and dependent on the training compartment with blockade only observed when conditioning was to the white/rough textured environment. This profile has also been reported for the serotonin (5-HT)3 receptor antagonist ondansetron. The CCKB antagonist L365-260 (0.000001-0.01 mg/kg) failed to antagonize the morphine CPP, if anything a mild potentiation was observed. To study this further we examined the interaction between L365-260 (0.01 mg/kg) and a subthreshold dose of morphine (0.3 mg/kg). At these doses neither drug elicited CPP, however when co-administered a significant CPP was recorded. Finally, L365-260 at 1 mg/kg induced a mild but significant CPP when administered alone. These results suggest a differential role of CCK receptor subtypes on reward-related behaviour and complement previous studies suggesting bimodal effects of CCK systems on mesolimbic dopamine function.
authors.affiliation: Clinical Psychopharmacology Program, Addiction Research Foundation, Toronto, Ontario, Canada.
authors.forename: G A
authors.initials: GA
authors.lastname: Higgins
authors.forename: P
authors.initials: P
authors.lastname: Nguyen
authors.forename: E M
authors.initials: EM
authors.lastname: Sellers
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D020109:Devazepide; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010671:Phenylurea Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D009270:Naloxone; C058121:L 365260; D012965:Sodium Chloride; D009020:Morphine; D020109:Devazepide