title: Involvement of glutamatergic N-methyl-d-aspartate receptors in the expression of increased head-dipping behaviors in the hole-board tests of olfactory bulbectomized mice.
abstract: Olfactory bulbectomized (OB) mice produce agitated anxiety-like behaviors in the hole-board test, which was expressed by an increase in head-dipping counts and a decrease in head-dipping latencies. However, the associated mechanisms remain unclear. In the present study, MK-801 (10, 100μg/kg), a selective N-methyl-d-aspartate (NMDA) receptor antagonist, significantly and dose-dependently suppressed the increased head-dipping behaviors in OB mice, without affecting sham mice. Similar results were obtained with another selective NMDA receptor antagonist D-AP5 treatment in OB mice. On the other hand, muscimol, a selective aminobutyric acid type A (GABAA) receptor agonist produced no effects on these hyperemotional behaviors in OB mice at a dose (100μg/kg) that produced anxiolytic-like effects in sham mice. Interestingly, glutamine contents and glutamine/glutamate ratios were significantly increased in the amygdala and frontal cortex of OB mice compared to sham mice. Based on these results, we concluded that the glutamatergic NMDA receptors are involved in the expression of increased head-dipping behaviors in the hole-board tests of OB mice. Accordingly, the changes in glutamatergic transmission in frontal cortex and amygdala may play important roles in the expression of these abnormal behaviors in OB mice.
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Hirose
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: asaitoh@ncnp.go.jp.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Saitoh
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Kamei
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage; D001007:Anxiety / Q000503:physiopathology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005625:Frontal Lobe / Q000378:metabolism; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D019416:Head Movements / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000008:administration & dosage; D009830:Olfactory Bulb / Q000601:surgery*; D011963:Receptors, GABA-A / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D009118:Muscimol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate
keywords: Amygdala; Animal model; Anxiety; Frontal cortex; Glutamate; Olfactory bulbectomy