Analysis of strain difference in behavior to Cholecystokinin (CCK) receptor mediated drugs in PVG hooded and Sprague-Dawley rats using elevated plus-maze test apparatus.
This study investigated the behavioral mechanisms underlying the anxiogenic, or anxiolytic mediated effects of CCK(2) receptor mediated agonist (CCK-4) and antagonist drugs (LY225910, LY288513, CR2945) in PVG hooded and Sprague-Dawley (SD) rats using the elevated plus maze test apparatus. In addition, the effects of a CCK(1) antagonist (CR1409) were investigated for its possible mediation in anxiety behavior between PVG hooded and SD rats. PVG hooded rats treated with CCK-4, decreased the time spent in the open arm and increased the time spent in the closed arm and correspondingly showed increase in the number of entries in the open arms while the number of entries in closed arm was insignificant, whereas SD rats decreased the time spent in the closed arm, while other parameters remained insignificant. PVG hooded rats administered with various CCK(2) antagonists (LY225910, LY288513, and CR2945) significantly increased the time spent in the open arm and correspondingly decreased the time spent in the closed arm, while the number of entries in the open or closed arm was insignificant, in contrast, SD rats failed to show any reliable significance. PVG hooded rats administered with the CCK(1) antagonist (CR1409), failed to show any reliable significance, in contrast, SD rats significantly increased the time spent in the open arm. The strain differences observed in this study suggests that CCK plays mainly as a neuromodulator, in which the various CCK(2) antagonists may not affect baseline anxiety state, but instead they modulate heightened states of anxiety through differential effects of CCK(1)/CCK(2) receptors.
Farook
J M
JM
Department of Pharmacology, Faculty of Medicine, National University of Singapore, 18 Medical Drive, Kent Ridge Cresent, 17597 Singapore, Singapore. farook@uthsca.edu
Zhu
Y Z
YZ
Wang
Q
Q
Moochhala
S M
SM
Lee
L
L
Wong
P T-H
PT
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018925:Chemokines / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D019742:Chemokines, CC; D002766:Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D052999:Quinazolinones; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013045:Species Specificity; D013758:Tetragastrin / Q000494:pharmacology
C435663:2-(2-(5-bromo-1H-indol-3-yl)ethyl)-3-(1-methylethoxyphenyl)-4-(3H)-quinazolinone; D014151:Anti-Anxiety Agents; C414047:CCL28 protein, human; C116183:CR 2945; D018925:Chemokines; D019742:Chemokines, CC; D011720:Pyrazoles; D011799:Quinazolines; D052999:Quinazolinones; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D001569:Benzodiazepines; C074681:1-(4-bromophenylaminocarbonyl)-4,5-diphenyl-3-pyrazolidinone; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide