Effect of NC-1900, an active fragment analog of arginine vasopressin, and inhibitors of arachidonic acid metabolism on performance of a passive avoidance task in mice.
In this study, we investigated the effect of administration of inhibitors of each of the arachidonic acid metabolism pathways and the effect of co-administration of these inhibitors with NC-1900, a fragment analog of arginine vasopressin, on step-through passive avoidance task performance. All drugs were administered just after the acquisition trial in the passive avoidance task. Intracerebroventricular (i.c.v.) administration of nordihydroguaiaretic acid (NDGA, 1 and 10 microg), a phospholipase A2 (PLA2) and lipoxygenase (LOX) inhibitor, and of arachidonyl trifluoromethyl ketone (ATK, 1 and 10 microg), a specific PLA2 inhibitor caused reductions in latency on the retention trial. The i.c.v. administration of either of baicalein (0.1-10 microg), a 12-LOX inhibitor, or AA-861 (0.1-10 microg), a 5-LOX inhibitor, did not influence the latency. Intraperitoneal administration of indomethacin (20 mg/kg), a non-specific COX inhibitor, or NS-398 (10 mg/kg), a specific COX-2 inhibitor, impaired performance on the retention trial in the task, while piroxicam (20 mg/kg), a specific COX-1 inhibitor, did not. Subcutaneous administration of NC-1900 (0.1 ng/kg) ameliorated the reduction of latency caused by NDGA, ATK, indomethacin, or NS-398. These results suggested that the COX-2 pathway of arachidonic acid metabolism may be important for learning and/or memory in the passive avoidance task in mice, and that the ameliorating effect of NC-1900, in part, is due to mimicking of the effects of metabolites of the COX-2 pathway.
Sato
Tomoaki
T
Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka-8, Kagoshima 890-8544, Japan. tomsato@dentb.hal.kagoshima-u.ac.jp
Ishida
Takayuki
T
Irifune
Masahiro
M
Tanaka
Koh-ichi
K
Hirate
Kenji
K
Nakamura
Norifumi
N
Nishikawa
Takashige
T
D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D004791:Enzyme Inhibitors; C115056:NC 1900; D009842:Oligopeptides; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D011761:Pyrrolidonecarboxylic Acid