Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of tropisetron: role of alpha7 nicotinic receptors.
We examined the effects of tropisetron, a 5-hydroxytryptamine (5-HT(3)) receptor antagonist and alpha7 nicotinic receptor agonist, on cognitive deficits in mice after repeated administration of the NMDA receptor antagonist phencyclidine (PCP). PCP (10 mg/kg/day for 10 days)-induced cognitive deficits were significantly improved by subsequent subchronic (2 weeks) administration of tropisetron, but not ondansetron. Effects of tropisetron were significantly antagonized by co-administration of the alpha7 nicotinic receptor antagonist methyllycaconitine, suggesting the role of alpha7 nicotinic receptors in the active mechanisms of tropisetron. These findings suggest that tropisetron could be a potential therapeutic drug for cognitive deficits in schizophrenic patients.
Hashimoto
Kenji
K
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan. hashimoto@faculty.chiba-u.jp
Fujita
Yuko
Y
Ishima
Tamaki
T
Hagiwara
Hiroko
H
Iyo
Masaomi
M
D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects; D007211:Indoles / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017294:Ondansetron / Q000494:pharmacology; D010622:Phencyclidine / Q000009:adverse effects; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D021641:Recognition, Psychology / Q000187:drug effects; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D000077526:Tropisetron; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D011978:Receptors, Nicotinic; D012702:Serotonin Antagonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; D017294:Ondansetron; D000077526:Tropisetron; D010622:Phencyclidine