Effects of galantamine on L-NAME-induced behavioral impairment in Y-maze task in mice.
Nitric oxide (NO) may play a role in the established processes of learning and memory. We examined the effects of N(omega)-nitro-L-arginine methylester (L-NAME), a nonselective inhibitor of NO synthase (NOS), on the performance of mice in a Y-maze task. L-NAME (100 mg/kg) markedly impaired spontaneous alternation behavior. However, galantamine (0.5 mg/kg) significantly attenuated this l-NAME-induced impairment. To clarify the molecular basis underlying galantamine's protective effects against L-NAME-induced impairment of spontaneous alternation behavior, we tested the ability of mecamylamine, an antagonist of nicotinic ACh receptor (nAChR), and scopolamine, an antagonist of muscarinic ACh receptor, to reduce galantamine's protective effects, and found that only the former had such an ability. Galantamine significantly also reduced L-NAME-induced decreases in NOx levels. However, mecamylamine cancelled galantamine's efficacy in countering the L-NAME-induced decrease in NOx levels. In the present study, we have determined that galantamine's protection against L-NAME-induced impairment of spontaneous alternation behavior in the Y-maze task might be mediated mainly by NOergic activation via the nAChR-related pathway.
Tanaka
Ken-ichi
K
Department of Clinical Pharmacy, Shujitsu University School of Pharmacy, Okayama, Japan. kntanaka@shujitsu.ac.jp
Yagi
Takao
T
Shimakoshi
Ryosuke
R
Azuma
Koji
K
Nanba
Takeshi
T
Ogo
Hiroya
H
Tamura
Akiko
A
Asanuma
Masato
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005702:Galantamine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D018697:Nootropic Agents / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D018733:Nicotinic Antagonists; D018697:Nootropic Agents; D005702:Galantamine; D009569:Nitric Oxide; D008464:Mecamylamine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester