Evidence for potentiation by CCK antagonists of the effect of cholecystokinin octapeptide in the elevated plus-maze.
Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 micrograms/kg, s.c.), a non-selective CCK agonist, decreased the exploratory activity of mice in an elevated plus-maze. At higher doses (5-10 micrograms/kg) CCK-8 reduced the frequency of rearing, but only 10 micrograms/kg of CCK-8 significantly inhibited the number of line crossings in the open-field test. A preferential CCKB antagonist L-365,260 (1 and 100 micrograms/kg, i.p.) and a non-selective CCK antagonist proglumide (0.1-1 microgram/kg, i.p.) potentiated the anti-exploratory effect of CCK-8 (2.5 micrograms/kg). Devazepide, a preferential CCKA antagonist, only at a high dose (100 micrograms/kg) tended to increase the action of CCK-8 in the plus-maze. However, the concomitant treatment of CCK-8 with L-365,260 and proglumide, differently from devazepide, also suppressed the locomotor activity in the open-field test. Therefore, it is likely that the potentiation by CCK antagonists of the anti-exploratory effect of CCK-8 is related to the suppression of motor activity. This peculiar interaction between CCK-8 and CCK antagonists could be explained in the light of the opposite role of CCKA and CCKB receptors in the regulation of motor activity in mice.
Vasar
E
E
Institute of Physiology, Tartu University, Estonia.
Lang
A
A
Harro
J
J
Bourin
M
M
Bradwejn
J
J
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010671:Phenylurea Compounds; D011377:Proglumide / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D011377:Proglumide; D020109:Devazepide; D012844:Sincalide