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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Inhibition of serotonin but not norepinephrine transport during development produces delayed, persistent perturbations of emotional behaviors in mice.
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Inhibition of serotonin but not norepinephrine transport during development produces delayed, persistent perturbations of emotional behaviors in mice.

机译：在发育过程中抑制5-羟色胺而不是去甲肾上腺素的转运会在小鼠中产生延迟的，持续的情绪行为扰动。

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Serotonin (5-HT) acts as a neurotransmitter, but also modulates brain maturation during early development. The demonstrated influence of genetic variants on brain function, personality traits, and susceptibility to neuropsychiatric disorders suggests a critical importance of developmental mechanisms. However, little is known about how and when developmentally perturbed 5-HT signaling affects circuitry and resulting behavior. The 5-HT transporter (5-HTT) is a key regulator of extracellular 5-HT levels and we used pharmacologic strategies to manipulate 5-HTT function during development and determine behavioral consequences. Transient exposure to the 5-HTT inhibitors fluoxetine, clomipramine, and citalopram from postnatal day 4 (P4) to P21 produced abnormal emotional behaviors in adult mice. Similar treatment with the norepinephrine transporter (NET) inhibitor, desipramine, did not adversely affect adult behavior, suggesting that 5-HT and norepinephrine (NE) do not share the same effects on brain development. Shifting our period of treatment/testing to P90/P185 failed to mimic the effect of earlier exposure, demonstrating that 5-HT effects on adult behavior are developmentally specific. We have hypothesized that early-life perturbations of 5-HT signaling affect corticolimbic circuits that do not reach maturity until the peri-adolescent period. In support of this idea, we found that abnormal behaviors resulting from postnatal fluoxetine exposure have a post-pubescent onset and persist long after reaching adult age. A better understanding of the underlying 5-HT sensitive circuits and how they are perturbed should lead to new insights into how various genetic polymorphisms confer their risk to carriers. Furthermore, these studies should help determine whether in utero exposure to 5-HTT blocking drugs poses a risk for behavioral abnormalities in later life.
机译：血清素（5-HT）充当神经递质，但在早期发育过程中也调节大脑成熟。遗传变异对脑功能，人格特质和对神经精神疾病的易感性的影响表明，发育机制至关重要。但是，关于5-HT信号如何以及何时受到发展影响会影响电路和所产生的行为，人们知之甚少。 5-HT转运蛋白（5-HTT）是细胞外5-HT水平的关键调节剂，我们使用药理学策略在发育过程中操纵5-HTT功能并确定行为后果。从出生后第4天（P4）到P21短暂暴露于5-HTT抑制剂氟西汀，氯米帕明和西酞普兰会在成年小鼠中产生异常的情绪行为。用去甲肾上腺素转运蛋白（NET）抑制剂地昔帕明进行的类似治疗不会对成年人的行为产生不利影响，这表明5-HT和去甲肾上腺素（NE）对大脑发育没有相同的作用。将我们的治疗/测试时间转移到P90 / P185不能模仿早期接触的影响，表明5-HT对成人行为的影响在发育上具有特异性。我们假设5-HT信号的早期生命干扰会影响皮质桥回路，这些回路直到青春期前才成熟。为了支持这一观点，我们发现，由产后氟西汀暴露引起的异常行为具有青春期后的发作，并在成年后持续很长时间。对潜在的5-HT敏感电路以及它们如何受到干扰的更好的理解应该导致对各种遗传多态性如何将其风险赋予携带者的新见解。此外，这些研究应有助于确定子宫内暴露于5-HTT阻断药物是否对以后的生活产生行为异常的危险。

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