Effects of mood stabilizers on marble-burying behavior in mice
Effects of mood stabilizers on marble-burying behavior in mice
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DOI：
10.1007/s00213-012-2904-9
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发表时间：
2013-03-01
影响因子：
3.4
通讯作者：
Fujiwara, Michihiro
中科院分区：
文献类型：
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作者：
Egashira, Nobuaki;Abe, Moe;Fujiwara, Michihiro
强迫症（OCD）的特征是反复出现不必要的想法（强迫症），通常伴有旨在减轻焦虑的重复行为（强迫症）。埋藏大理石行为是研究强迫症的一种药理学模型。在本研究中，我们研究了情绪稳定剂对小鼠埋藏大理石行为的影响，以及GABA受体在这种行为中的作用。评价了丙戊酸盐、卡马西平、碳酸锂、拉莫三嗪、蝇蕈醇和巴氯芬对小鼠埋藏大理石行为的影响。丙戊酸盐、卡马西平、碳酸锂和巴氯芬对小鼠埋藏大理石行为的影响。（10、30和100 mg/kg，i.p.）和卡马西平（30和100 mg/kg，p.o.）显著减少了ICR小鼠的大理石埋藏行为，而不影响总的运动活性。拉莫三嗪（30 mg/kg，i. p.）也显著降低ddY小鼠的大理石埋藏行为。另一方面，碳酸锂（10、30和100 mg/kg，i. p.）减少ddY小鼠的总运动活动而不影响大理石埋藏行为。选择性GABA（A）受体激动剂蝇蕈醇（1 mg/kg）显著降低了大理石埋藏行为而不影响总的运动活性，而选择性GABA（B）受体激动剂巴氯芬（3 mg/kg）降低了总的运动活性而不影响大理石埋藏行为。GABA（A）受体拮抗剂荷包牡丹碱（3 mg/kg）可显著对抗蝇蕈醇（1 mg/kg）和丙戊酸钠（100 mg/kg）引起的大鼠大理石埋藏行为的减少，提示GABA能机制参与了大理石埋藏行为的形成，丙戊酸钠、卡马西平和拉莫三嗪均能减少大理石埋藏行为。此外，丙戊酸盐通过GABA（A）受体依赖性机制减少大理石埋藏行为。
Obsessive-compulsive disorder (OCD) is characterized by recurrent unwanted thoughts (obsessions), usually accompanied by repetitive behaviors (compulsions) intended to alleviate anxiety. Marble-burying behavior is a pharmacological model for study of OCD.In the present study, we examined the effects of mood stabilizers on marble-burying behavior in mice, as well as the role of GABA receptors in this behavior.The effects of treatment with valproate, carbamazepine, lithium carbonate, lamotrigine, muscimol and baclofen on marble-burying behavior in mice were evaluated.Valproate (10, 30 and 100 mg/kg, i.p.) and carbamazepine (30 and 100 mg/kg, p.o.) significantly reduced marble-burying behavior without affecting total locomotor activity in ICR mice. Lamotrigine (30 mg/kg, i.p.) also significantly reduced marble-burying behavior in ddY mice. On the other hand, lithium carbonate (10, 30 and 100 mg/kg, i.p.) reduced total locomotor activity without affecting marble-burying behavior in ddY mice. The selective GABA(A) receptor agonist muscimol (1 mg/kg) significantly reduced marble-burying behavior without affecting total locomotor activity, whereas the selective GABA(B) receptor agonist baclofen (3 mg/kg) reduced total locomotor activity without affecting marble-burying behavior. Moreover, the selective GABA(A) receptor antagonist bicuculline (3 mg/kg) significantly counteracted the decrease in marble-burying induced by the administration of muscimol (1 mg/kg) and valproate (100 mg/kg).These results suggest that GABAergic mechanism is involved in marble-burying behavior, and that valproate, carbamazepine and lamotrigine reduce marble-burying behavior. Moreover, valproate reduces marble-burying behavior via a GABA(A) receptor-dependent mechanism.