Distinct Circuits Underlie the Effects of 5-HT1B Receptors on Aggression and Impulsivity.
Distinct Circuits Underlie the Effects of 5-HT1B Receptors on Aggression and Impulsivity.
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DOI：
10.1016/j.neuron.2015.03.041
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发表时间：
2015-05-06
期刊：
影响因子：
16.2
通讯作者：
Ahmari, Susanne E.
中科院分区：
文献类型：
--
作者：
Nautiyal, Katherine M.;Tanaka, Kenji F.;Barr, Mary M.;Tritschler, Laurent;Le Dantec, Yannick;David, Denis J.;Gardier, Alain M.;Blanco, Carlos;Hen, Rene;Ahmari, Susanne E.
冲动和攻击性行为都是由β-羟色胺能信号调节的，特别是通过5-羟色胺1B受体（5-HT 1BR）。5-HT 1BR基因敲除小鼠表现出更强的攻击性和冲动性，5-HT 1BR多态性与人类的攻击性和药物成瘾有关。为了剖析5-HT 1BR影响这些表型的机制，我们开发了一种小鼠模型来空间和时间调节5-HT 1BR表达。我们的研究结果表明，前脑5-HT 1B异源受体在出生后早期期间表达的神经系统的发展，成人侵略的基础。然而，不同的异源受体在成年期的行为参与调解冲动。与冲动性相关，在缺乏5-HT 1BRs的情况下，丘脑核中的多巴胺升高，并在成年后恢复受体后正常化。总的来说，这些数据表明，虽然青少年5-HT 1BRs的表达影响攻击性行为，但一组独特的5-HT 1B受体在成年期调节冲动行为。
Impulsive and aggressive behaviors are both modulated by serotonergic signaling, specifically through the serotonin 1B receptor (5-HT1BR). 5-HT1BR knockout mice show increased aggression and impulsivity, and 5-HT1BR polymorphisms are associated with aggression and drug addiction in humans. To dissect the mechanisms by which the 5-HT1BR affects these phenotypes, we developed a mouse model to spatially and temporally regulate 5-HT1BR expression. Our results demonstrate that forebrain 5-HT1B heteroreceptors expressed during an early postnatal period contribute to the development of the neural systems underlying adult aggression. However, distinct heteroreceptors acting during adulthood are involved in mediating impulsivity. Correlating with the impulsivity, dopamine in the nucleus accumbens is elevated in the absence of 5-HT1BRs, and normalized following adult rescue of the receptor. Overall, these data show that while adolescent expression of 5-HT1BRs influences aggressive behavior, a distinct set of 5-HT1B receptors modulate impulsive behavior during adulthood.
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