Changes in motor activity and forebrain [propionyl-3H]propionylated-CCK-8 binding in mice after repeated administration of drugs affecting cholecystokinin receptors.
The effects of acute or repeated treatment of male albino BKW mice with caerulein, a cholecystokinin octapeptide (CCK-8) agonist, and with devazepide (MK-329) and L-365,260, antagonists at CCKA ('peripheral') and CCKB ('central') receptors respectively, on motor activity and [propionyl-3H]propionylated-CCK-8 ([3H]pCCK-8) binding were studied. Acute treatment with a large dose of caerulein (100 micrograms/kg s.c.) suppressed motor activity (line crossings and rearings) whereas devazepide (2 mg/kg i.p.) had the opposite action. L-365,260 (2 mg/kg i.p.) increased only the number of rearings. Tolerance developed to the locomotor effects of caerulein and devazepide when these same doses were administered once daily (caerulein) or twice daily (devazepide) for 10 days. Twice daily administration of L-365,260 (2 mg/kg) for 10 days did not significantly alter the locomotor activity of mice. The sedative effect of caerulein (20 micrograms/kg s.c.) was markedly reduced in mice receiving repeated injections of either a larger amount of caerulein (100 micrograms/kg) or devazepide but not after L-365,260. The stimulant effect of (+)-amphetamine (2 mg/kg s.c.) on motor activity was increased by subchronic administration of either devazepide or caerulein, but not by L-365,260. All three compounds (caerulein, devazepide and L-365,260) increased the number of [( 3H]pCCK-8 binding sites in mouse forebrain but the increase was only significant after L-365,260. The effects of long-term treatment with caerulein are probably related to the stimulation of CCKA receptors, whereas the paradoxically similar action of devazepide may be linked to the blockade of both subtypes of the CCK-8 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Vasar
E
E
Psychopharmacology Laboratory, Tartu University, Estonia, U.K.
Stephenson
J D
JD
Meldrum
B S
BS
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020109:Devazepide; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010671:Phenylurea Compounds; D016548:Prosencephalon / Q000187:drug effects*; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D012844:Sincalide / Q000378:metabolism*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002108:Ceruletide; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide