Suppression of conditioned fear by administration of CCKB receptor antagonist PD135158.
In order to examine the involvement of CCK in the formation of anxiety, we have investigated whether CCKB receptor antagonist PD135158 suppressed conditioned fear stress. Rats were individually subjected to 30 min of inescapable electric footshock in a chamber with a grid floor. First, the rats were individually subjected to 30 min of footshock. Twenty-four h after the footshock, the rats were again placed in the chamber and observed for 5 min without shocks. PD135158 was administered 30 min before placing the rats in the chamber again. Secondly, PD135158 was administered 30 min before footshock. Thirdly, PD135158 was administered 5 min after footshock. Administration of PD135158 30 min before conditioned fear stress significantly reduced freezing behavior. Administration of PD135158 30 min before footshock also significantly reduced freezing behavior. But, administration of PD135158 5 min after footshock did not significantly reduce freezing behavior. PD135158 blocked not only the acquisition but also the expression of conditioned fear. These results suggest that the CCKB receptor might play an important role in conditioned fear stress and that it might be related to anxiety.
Tsutsumi
T
T
Department of Neuropsychiatry, Oita Medical University, Hasama-machi, Oita, Japan.
Akiyoshi
J
J
Isogawa
K
K
Kohno
Y
Y
Hikichi
T
T
Nagayama
H
H
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy; D001923:Brain Chemistry / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D004597:Electroshock; D005239:Fear / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D016584:Panic Disorder / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; D007211:Indoles; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C065600:PD 135158; D008536:Meglumine