Opposing effects of NMDA receptor antagonists on early life stress-induced aggression in mice.
Opposing effects of NMDA receptor antagonists on early life stress-induced aggression in mice.
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DOI：
10.1002/ab.22022
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发表时间：
2022-05
影响因子：
2.9
通讯作者：
Li, Zheng
中科院分区：
文献类型：
--
作者：
Nordman, Jacob C.;Bartsch, Caitlyn J.;Li, Zheng
儿童创伤的发生率在经常再犯的暴力罪犯中很高。很少有临床选择可用于治疗与儿童创伤相关的过度和反复发生的暴力攻击。那些确实存在的药物大多无效，而且往往充满副作用。一个有前途的药理学靶点是谷氨酸结合N-甲基-d-天冬氨酸受体（NMDAR）。临床上可用的NMDAR拮抗剂已被证明成功地减轻与许多精神疾病相关的暴力和攻击行为，并对神经系统功能和行为具有即时和长期影响。本研究考察了三种NMDAR拮抗剂对早期生活应激引起的持久攻击性的影响：MK-801，美金刚胺和氯胺酮。我们发现，在青春期早期的社会隔离，随后在青春期后期的非偶然性足部休克（FS）的形式急性创伤性应激反应，协同工作，以促进长期持续的过度侵略小鼠时，测量1周后。FS前30分钟全身注射MK-801和美金刚胺抑制了我们的早期生活应激诱导方案诱导的持久攻击行为。另一方面，在FS之前全身注射氯胺酮显著增强了持久的攻击行为。这些发现表明，MK-801、美金刚和氯胺酮对生命早期应激诱导的攻击性具有不同和相反的作用，表明这些药物可能在机制上不同。这项研究确定美金刚胺作为一种有前途的药物治疗与早期生活压力相关的攻击性行为，并证明需要更大的照顾时，使用谷氨酸受体拮抗剂治疗攻击。
Rates of childhood trauma are high amongst violent offenders who frequently recidivate. Few clinical options are available to treat excessive and recurring violent aggression associated with childhood trauma. Those that do exist are largely ineffective and often replete with side effects. One promising pharmacological target is the glutamate binding N-methyl-d-aspartate receptor (NMDAR). Clinically available NMDAR antagonists have proven successful in mitigating violent and aggressive behavior associated with a host of psychiatric diseases and have both immediate and long-term effects on nervous system function and behavior. This study examined the impact of three NMDAR antagonists on long-lasting aggression brought on by early-life stress: MK-801, memantine, and ketamine. We find that social isolation early in adolescence followed by acute traumatic stress in the form of noncontingent foot shock (FS) late in adolescence works in tandem to promote long-lasting excessive aggression in mice when measured 1 week later. Systemic injections of MK-801 and memantine 30 min before FS suppressed the long-lasting attack behavior induced by our early life stress induction protocol. Systemic injections of ketamine, on the other hand, significantly enhanced the long-lasting attack behavior when injected before FS. These findings indicate that MK-801, memantine, and ketamine have distinct and opposing effects on early life stress-induced aggression, suggesting these drugs may be mechanistically distinct. This study identifies memantine as a promising pharmacological treatment for aggressive behavior associated with early life stress and demonstrates the need for greater care when using glutamate receptor antagonists to treat aggression.
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影响因子：
3.1
作者：
Anjomshoa, Maryam;Boroujeni, Shakiba N.;Amini-Khoei, Hossein
通讯作者：
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影响因子：
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5.6
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影响因子：
6.7
作者：
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通讯作者：
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影响因子：
2.5
作者：
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通讯作者：
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