Yan Bin, He Jue, Xu Haiyun, Zhang Yanbo, Bi Xiaoying, Thakur Sonia, Gendron Alain, Kong Jiming, Li Xin-Min
Neuropsychiatry Research Unit, Department of Psychiatry, College of Medicine, University of Saskatchewan, 103 Wiggins Road, Saskatoon, SK S7N 5E4, Canada.
Behav Brain Res. 2007 Aug 22;182(1):36-41. doi: 10.1016/j.bbr.2007.05.002. Epub 2007 May 7.
Recently, we have reported that quetiapine, an atypical antipsychotic drug, prevents memory impairment and hippocampus neurodegeneration induced by global cerebral ischemia (GCI). In the present study, we examined the possible effects of quetiapine on other behavioural deficits, including the depressive and anxiolytic-like behavioural consequences of GCI. Mice were treated with quetiapine (5 or 10mg/kg/day; intraperitoneal (i.p.)) for 14 days. On Day 15, the animals were subjected to GCI. GCI resulted in a decrease of striatal tyrosine hydroxylase (TH) immunostaining and induced depressive and anxiolytic-like behavioural changes. The behavioural changes were indicated by a significant increase in the immobility duration in a tail-suspension test, and an increase in the time spent in the light box in a light/dark box test. Pre-administration of quetiapine significantly alleviated the decreased TH immunostaining and attenuated the depressive and anxiolytic-like behavioural changes induced by GCI. These results enhance our understanding about the mechanisms of quetiapine and suggest a wider perspective for the clinical use of quetiapine.
最近，我们报道了非典型抗精神病药物喹硫平可预防全脑缺血（GCI）诱导的记忆障碍和海马神经变性。在本研究中，我们研究了喹硫平对其他行为缺陷的可能影响，包括GCI的抑郁样和抗焦虑样行为后果。小鼠接受喹硫平（5或10mg/kg/天；腹腔注射（i.p.））治疗14天。在第15天，对动物进行全脑缺血处理。全脑缺血导致纹状体酪氨酸羟化酶（TH）免疫染色减少，并诱导抑郁样和抗焦虑样行为变化。行为变化通过悬尾试验中不动时间的显著增加以及明暗箱试验中在明箱中停留时间的增加来表明。预先给予喹硫平可显著减轻TH免疫染色的减少，并减轻全脑缺血诱导的抑郁样和抗焦虑样行为变化。这些结果增进了我们对喹硫平作用机制的理解，并为喹硫平的临床应用提供了更广阔的视角。
