Opposite effects mediated by CCKA and CCKB receptors in behavioural and hormonal studies in rats.
We compared the influence of two cholecystokinin (CCK) antagonists, devazepide and L-365,260 [3R-(+)-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3y l)-N'-(3-methyl-phenyl)urea], upon two distinct phenomena, behavioural and hormonal effects of caerulein (5 micrograms/kg s.c.), and unselective CCK agonist, in rats. Behavioural effects were assessed in the elevated plus-maze and open field tests. In separate experiments, effects on thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) levels in serum of male rats were studied. Caerulein inhibited the exploratory behaviour in the plus-maze. Time spent in the open part, the number of line crossings and closed arm entries were significantly decreased, whereas the ratio of failed attempts/closed arm entries was increased. The anti-exploratory effect of caerulein was antagonized by the pretreatment with L-365,260 (10 micrograms/kg), a preferential antagonist at CCKB receptors, but was increased by devazepide (1-100 micrograms/kg), a preferential CCKA antagonist. L-365,260 (1-100 micrograms/kg) and devazepide (1-100 micrograms/kg) given alone did not change the behaviour of rats in the plus-maze test. Caerulein (5 micrograms/kg) itself did not modify the locomotor activity of rats in open field. However, the concomitant administration of caerulein with devazepide (1-10 micrograms/kg) reduced the frequency of line crossings and rearings. In the hormonal studies caerulein significantly decreased the cold-induced increase of TSH levels in serum. GH and PRL levels were not markedly affected by caerulein.(ABSTRACT TRUNCATED AT 250 WORDS)
Männistö
P T
PT
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Lang
A
A
Harro
J
J
Peuranen
E
E
Bradwejn
J
J
Vasar
E
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001570:Benzodiazepinones / Q000494:pharmacology*; D002108:Ceruletide / Q000008:administration & dosage / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010671:Phenylurea Compounds; D011388:Prolactin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013972:Thyrotropin / Q000097:blood
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002108:Ceruletide; D011388:Prolactin; D013972:Thyrotropin; D002766:Cholecystokinin; D020109:Devazepide