COBRE: UMMC: NEUROBEHAV EFFECTS OF EARLY EXPOSURE TO PSYCHOTHERAPEUTIC AGENTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。本研究的重点是早期接触选择性5-羟色胺再摄取抑制剂(SSRI)抗抑郁药对大脑发育和行为的影响。SSRIs是孕妇和哺乳母亲的首选药物疗法，最近的研究表明，胎儿和哺乳婴儿暴露在与母亲相似的药物浓度中。关于早期SSRI暴露的长期神经生物学影响，人们知之甚少。然而，最近的研究表明，这种暴露可能会持续增加人类的应激性，并损害人类的精细运动行为和疼痛敏感性。在早期接触抗抑郁药物的啮齿动物模型中，已经注意到男性性行为和攻击性反应的持久损害。我们最近已经证明，早期接触抗抑郁药物的行为效应也是由高度选择性的SSRI产生的。此外，这种暴露会导致色氨酸羟化酶和5-羟色胺转运体的表达永久减少，这两种蛋白是调节5-羟色胺能回路的关键蛋白质。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This research is focused on the effects of early exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants on brain development and behavior. SSRIs are the pharmacotherapy of choice for pregnant and nursing mothers and recent studies have demonstrated that the fetus and nursing infant are exposed to drug concentrations similar to those of the mother. Little is known about the long-term neurobiological effects of early SSRI exposure however, recent studies indicate that such exposure may have lasting increases in irritability and impairment of fine motor behavior and pain sensitivity in humans. In rodent models of early antidepressant exposure, lasting impairment of male sexual behavior and aggressive response has been noted. We have recently demonstrated that the behavioral effects of early antidepressant exposure are also produced by highly selective SSRIs. Moreover, such exposure results in permanent reductions in the expression of tryptophan hydroxylase and the serotonin transporter which are critical proteins regulating serotonergic circuits