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

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70 Citations (Scopus)


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
Issue number1-3
Publication statusPublished - May 31 2008

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Pharmacology


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