Effects of glutamate-related drugs on marble-burying behavior in mice: Implications for obsessive-compulsive disorder

Nobuaki Egashira, Ryoko Okuno, Satoko Harada, Michihiko Matsushita, Kenichi Mishima, Katsunori Iwasaki, Ryoji Nishimura, Ryozo Oishi, Michihiro Fujiwara

Research output: Contribution to journalArticle

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Abstract

Clinical evidence demonstrates altered glutamatergic neurotransmission in patients suffering from obsessive-compulsive disorder (OCD). We examined the effects of glutamate-related drugs on marble-burying behavior, which is an animal model of OCD. The uncompetitive N-methyl-d-aspartate (NMDA) antagonists memantine (10 mg/kg, i.p.) and amantadine (30 mg/kg, i.p.) significantly inhibited marble-burying behavior without affecting locomotor activity in mice. Similarly, the uncompetitive NMDA receptor antagonist 5R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine hydrogen maleate (MK-801, 0.3 mg/kg, i.p.) inhibited marble-burying behavior. However, MK-801 at the same dose markedly increased locomotor activity. By contrast, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX) and the glutamate release inhibitor riluzole showed no effect on marble-burying behavior and significant suppression of locomotor activity. MK-801 (0.3 mg/kg, i.p.) and memantine (10 mg/kg, i.p.) significantly disrupted prepulse inhibition as an operational measure of sensorimotor gating. By contrast, amantadine (30 mg/kg, i.p.) did not affect prepulse inhibition. These findings suggest that amantadine could be a useful drug for the treatment of OCD.

Original languageEnglish
Pages (from-to)164-170
Number of pages7
JournalEuropean Journal of Pharmacology
Volume586
Issue number1-3
DOIs
Publication statusPublished - May 31 2008

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Calcium Carbonate
Obsessive-Compulsive Disorder
Amantadine
Dizocilpine Maleate
Glutamic Acid
Locomotion
Memantine
Pharmaceutical Preparations
Riluzole
Sensory Gating
Imines
AMPA Receptors
Sulfonamides
Aspartic Acid
Synaptic Transmission
Animal Models
Prepulse Inhibition
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Effects of glutamate-related drugs on marble-burying behavior in mice : Implications for obsessive-compulsive disorder. / Egashira, Nobuaki; Okuno, Ryoko; Harada, Satoko; Matsushita, Michihiko; Mishima, Kenichi; Iwasaki, Katsunori; Nishimura, Ryoji; Oishi, Ryozo; Fujiwara, Michihiro.

In: European Journal of Pharmacology, Vol. 586, No. 1-3, 31.05.2008, p. 164-170.

Research output: Contribution to journalArticle

Egashira, N, Okuno, R, Harada, S, Matsushita, M, Mishima, K, Iwasaki, K, Nishimura, R, Oishi, R & Fujiwara, M 2008, 'Effects of glutamate-related drugs on marble-burying behavior in mice: Implications for obsessive-compulsive disorder', European Journal of Pharmacology, vol. 586, no. 1-3, pp. 164-170. https://doi.org/10.1016/j.ejphar.2008.01.035
Egashira, Nobuaki ; Okuno, Ryoko ; Harada, Satoko ; Matsushita, Michihiko ; Mishima, Kenichi ; Iwasaki, Katsunori ; Nishimura, Ryoji ; Oishi, Ryozo ; Fujiwara, Michihiro. / Effects of glutamate-related drugs on marble-burying behavior in mice : Implications for obsessive-compulsive disorder. In: European Journal of Pharmacology. 2008 ; Vol. 586, No. 1-3. pp. 164-170.
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