Effect of donepezil on group II mGlu receptor agonist- or antagonist-induced amnesia on passive avoidance in mice.
We examined the effect of the acetylcholinesterase (AChE) inhibitor, donepezil hydrocloride (DONP), on group II metabotropic glutamate (mGlu) receptor agonist- or antagonist-induced amnesia in the step-through passive avoidance task in male mice. DCG-IV, a group II mGlu receptor agonist, at dose of 50 ng and LY341495, a group II mGlu receptor antagonist, at dose of 300 ng, significantly attenuated the latency on the step-through task. The subcutaneous injection of DONP at dose of 1 mg/kg 1 hour before passive avoidance performance ameliorated the amnesia induced by DCG-IV and LY341495, whereas donepezil alone did not affect task latency. The results suggest that activation of group II mGlu receptors and disinhibition of the cAMP/PKA signaling pathway (caused by group II mGlu receptor antagonist) have a negative action on step-through passive avoidance memory performance, and that group II mGlu receptors and ACh interact to modulate learning and memory function.
Sato
Tomoaki
T
Department of Applied Pharmacology, Kagoshima University Graduate School of Medical & Dental Sciences, Sakuragaoka, Kagoshima 890-8544, Japan. tomsato@dentb.hal.kagoshima-u.ac.jp
Tanaka
Koh-ichi
K
Ohnishi
Yoshiko
Y
Irifune
Masahiro
M
Nishikawa
Takashige
T
D000596:Amino Acids / Q000494:pharmacology; D000647:Amnesia / Q000139:chemically induced* / Q000517:prevention & control*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology; D000077265:Donepezil; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors*; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D002800:Cholinesterase Inhibitors; D003521:Cyclopropanes; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; C114624:LY 341495; D018697:Nootropic Agents; D010880:Piperidines; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D000077265:Donepezil; D005998:Glycine