慢性抗精神病药物治疗对多巴胺转运体敲低小鼠的躁狂样行为的影响有限。
Chronic antipsychotic treatment exerts limited effects on the mania-like behavior of dopamine transporter knockdown mice.
机构信息
Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States.
Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States; Center of Excellence for Stress and Mental Health and Research Service, VA San Diego Healthcare System, United States.
出版信息
Behav Brain Res. 2021 May 7;405:113167. doi: 10.1016/j.bbr.2021.113167. Epub 2021 Feb 9.
BACKGROUND
Bipolar disorder is a life-threatening disorder linked to dopamine transporter (DAT) polymorphisms, with reduced DAT levels seen in positron emission tomography and postmortem brains.
AIMS
The purpose of this study was to examine the effects of approved antipsychotics on DAT dysfunction-mediated mania behavior in mice.
METHODS
DAT knockdown mice received either D-family receptor antagonist risperidone or asenapine and mania-related behaviors were assessed in the clinically-relevant behavioral pattern monitor to assess spontaneous exploration.
RESULTS
Chronic risperidone did not reverse mania-like behavior in DAT knockdown mice. Chronic asenapine reduced mania behavior but this effect was more pronounced in wild-type littermates than in DAT knockdown mice.
CONCLUSION
Taken together, these findings suggest that while acute antipsychotic treatment may be beneficial in management of bipolar mania, more targeted therapeutics may be necessary for long-term treatment. Specific investigation into DAT-targeting drugs could improve future treatment of bipolar mania.
背景
双相情感障碍是一种危及生命的疾病，与多巴胺转运体（DAT）多态性有关，正电子发射断层扫描和尸检大脑中可见 DAT 水平降低。
目的
本研究旨在探讨已批准的抗精神病药物对小鼠 DAT 功能障碍介导的躁狂行为的影响。
方法
DAT 敲低小鼠接受 D 家族受体拮抗剂利培酮或阿塞那平治疗，并在临床相关的行为模式监测器中评估躁狂相关行为，以评估自发探索。
结果
慢性利培酮不能逆转 DAT 敲低小鼠的躁狂样行为。慢性阿塞那平可减少躁狂行为，但在野生型同窝仔鼠中比在 DAT 敲低小鼠中更为明显。
结论
总之，这些发现表明，虽然急性抗精神病药物治疗可能对双相躁狂症的管理有益，但可能需要更有针对性的治疗方法进行长期治疗。对 DAT 靶向药物的具体研究可以改善双相躁狂症的未来治疗。
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