Effects of agents targeting glutamatergic systems on marble-burying behavior.
Accumulating evidence has implicated glutamatergic systems in psychiatric disorders. Abnormalities in glutamatergic systems have consistently been identified in obsessive-compulsive disorder (OCD). Marble-burying behavior has been described in literature as a potentially useful measure for modeling OCD in mice. However, involvement of glutamatergic systems in marble-burying behavior has largely remained unexplored. Here, the effects of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiator, CX546, and an NR2B subunit-containing N-methyl-D-aspartate (NMDA) receptor antagonist, Ro25-6981, were examined using a marble-burying test. Treatment with highest dose (30.0mg/kg) of CX546 significantly inhibited the marble-burying behavior. Moreover, treatment with Ro25-6981 also significantly reduced the marble-burying behavior. In contrast, both drugs did not affect locomotor activity in mice. The present results suggest that glutamatergic systems might be related to marble-burying behavior. Furthermore, agents targeting glutamateric systems such as an AMPA receptor potentiator and an NR2B receptor antagonist, may be useful in treating OCD.
Iijima
Michihiko
M
Discovery Pharmacology, Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
Kurosu
Shinsuke
S
Chaki
Shigeyuki
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004149:Dioxoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
C443080:1-(1,4-benzodioxan-6-ylcarbonyl)piperidine; D004149:Dioxoles; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981