Effects of NMDA receptor-related agonists on learning and memory impairment in olfactory bulbectomized mice.
A significant impairment of learning and memory-related behavior was induced in mice on the 7th and 14th days after olfactory bulbectomy (OBX), as measured by a passive avoidance task. The involvement of the N-methyl-D-aspartate (NMDA) receptor ion-channel complex for learning and memory-related behavior impairment was examined by the intracerebroventricular administration of several NMDA receptor-related agonists and in combination with antagonists. The NMDA receptor agonist NMDA (1 ng/mouse) and the polyamine site agonist spermidine (1 micro g/mouse) improved learning and memory-related behavior impairment. In contrast, the glycine agonist D-cycloserine (0.2, 1 and 5 micro g/mouse) had no effect on learning and memory-related behavior impairment. The improved effects by NMDA and spermidine were reversed by the coadministration of D-APV, a competitive NMDA receptor antagonist, MK-801, an NMDA ion-channel blocker and ifenprodil, a polyamine site antagonist, respectively. These results suggest that the degeneration of NMDA receptors and polyamine sites in the NMDA receptor ion-channel complex may be involved in the OBX-induced impairment of learning and memory-related behavior.
Tadano
T
T
Department of Pharmacology, Tohoku Pharmaceutical University, Sendai, Japan. tadano@tohoku-pharm.ac.jp
Hozumi
S
S
Yamadera
F
F
Murata
A
A
Niijima
F
F
Tan-No
K
K
Nakagawasai
O
O
Kisara
K
K
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D003523:Cycloserine / Q000008:administration & dosage; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004359:Drug Therapy, Combination; D007276:Injections, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D009830:Olfactory Bulb / Q000503:physiopathology / Q000601:surgery*; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000502:physiology / Q000627:therapeutic use*; D013095:Spermidine / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D003523:Cycloserine; C010739:ifenprodil; D013095:Spermidine