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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究的重点是早期暴露于选择性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是孕妇和哺乳期母亲的首选药物治疗，最近的研究表明，胎儿和哺乳期婴儿暴露于与母亲相似的药物浓度。关于早期SSRI暴露的长期神经生物学效应知之甚少，然而，最近的研究表明，这种暴露可能会持续增加人类的易怒和精细运动行为和疼痛敏感性的损害。在早期抗抑郁药暴露的啮齿动物模型中，已注意到雄性性行为和攻击性反应的持久损害。我们最近证明，早期抗抑郁药暴露的行为效应也是由高选择性SSRIs产生的。此外，这种暴露导致色氨酸羟化酶和5-羟色胺转运蛋白表达的永久性减少，这两种蛋白是调节多巴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