Discovery Pharmacology, Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
Neurosci Lett. 2010 Mar 3;471(2):63-5. doi: 10.1016/j.neulet.2009.12.048. Epub 2009 Dec 28.
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.
越来越多的证据表明谷氨酸能系统与精神疾病有关。在强迫症(OCD)中,谷氨酸能系统的异常一直被发现。埋 Marble 行为在文献中被描述为一种在小鼠中模拟 OCD 的有用方法。然而,谷氨酸能系统在埋 Marble 行为中的参与在很大程度上仍未得到探索。在这里,使用 Marble 埋埋测试研究了一种 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 受体增效剂 CX546 和一种含有 NR2B 亚基的 N-甲基-D-天冬氨酸 (NMDA) 受体拮抗剂 Ro25-6981 的作用。CX546 的最高剂量(30.0mg/kg)治疗显著抑制了 Marble 埋埋行为。此外,Ro25-6981 治疗也显著减少了 Marble 埋埋行为。相比之下,这两种药物均不影响小鼠的运动活性。目前的结果表明,谷氨酸能系统可能与 Marble 埋埋行为有关。此外,针对谷氨酸能系统的药物,如 AMPA 受体增效剂和 NR2B 受体拮抗剂,可能对治疗 OCD 有用。