Nautiyal Katherine M, Tanaka Kenji F, Barr Mary M, Tritschler Laurent, Le Dantec Yannick, David Denis J, Gardier Alain M, Blanco Carlos, Hen René, Ahmari Susanne E
Department of Psychiatry, Columbia University, New York, NY 10032, USA; Division of Integrative Neuroscience, the New York State Psychiatric Institute, New York, NY 10032, USA.
Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo 160 8582, Japan.
Neuron. 2015 May 6;86(3):813-26. doi: 10.1016/j.neuron.2015.03.041. Epub 2015 Apr 16.
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 modulates impulsive behavior during adulthood.
冲动和攻击行为均受血清素能信号传导调节，具体是通过血清素1B受体（5-HT1BR）。5-HT1BR基因敲除小鼠表现出攻击性和冲动性增加，且5-HT1BR基因多态性与人类的攻击性和药物成瘾有关。为了剖析5-HT1BR影响这些表型的机制，我们构建了一个小鼠模型，用于在空间和时间上调节5-HT1BR的表达。我们的结果表明，出生后早期表达的前脑5-HT1B异受体有助于成年期攻击行为背后的神经系统发育。然而，成年期起作用的不同异受体参与介导冲动性。与冲动性相关的是，在缺乏5-HT1BR的情况下，伏隔核中的多巴胺水平升高，而在成年期受体得到挽救后恢复正常。总体而言，这些数据表明，虽然5-HT1BR的青春期表达影响攻击行为，但一组不同的5-HT1B受体在成年期调节冲动行为。
