Altieri Stefanie C, Yang Hongyan, O'Brien Hannah J, Redwine Hannah M, Senturk Damla, Hensler Julie G, Andrews Anne M
1] Semel Institute for Neuroscience and Human Behavior and Hatos Center for Neuropharmacology, David Geffen School of Medicine, and California NanoSystems Institute, University of California, Los Angeles, CA, USA [2] Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA.
Semel Institute for Neuroscience and Human Behavior and Hatos Center for Neuropharmacology, David Geffen School of Medicine, and California NanoSystems Institute, University of California, Los Angeles, CA, USA.
Neuropsychopharmacology. 2015 May;40(6):1456-70. doi: 10.1038/npp.2014.331. Epub 2014 Dec 19.
Large numbers of women undergo antidepressant treatment during pregnancy; however, long-term consequences for their offspring remain largely unknown. Rodents exposed to serotonin transporter (SERT)-inhibiting antidepressants during development show changes in adult emotion-like behavior. These changes have been equated with behavioral alterations arising from genetic reductions in SERT. Both models are highly relevant to humans yet they vary in their time frames of SERT disruption. We find that anxiety-related behavior and, importantly, underlying serotonin neurotransmission diverge between the two models. In mice, constitutive loss of SERT causes life-long increases in anxiety-related behavior and hyperserotonemia. Conversely, early exposure to the antidepressant escitalopram (ESC; Lexapro) results in decreased anxiety-related behavior beginning in adolescence, which is associated with adult serotonin system hypofunction in the ventral hippocampus. Adult behavioral changes resulting from early fluoxetine (Prozac) exposure were different from those of ESC and, although somewhat similar to SERT deficiency, were not associated with changes in hippocampal serotonin transmission in late adulthood. These findings reveal dissimilarities in adult behavior and neurotransmission arising from developmental exposure to different widely prescribed antidepressants that are not recapitulated by genetic SERT insufficiency. Moreover, they support a pivotal role for serotonergic modulation of anxiety-related behavior.
大量女性在孕期接受抗抑郁治疗；然而，其后代的长期影响在很大程度上仍不为人知。在发育过程中接触血清素转运体（SERT）抑制性抗抑郁药的啮齿动物，成年后会出现类似情绪的行为变化。这些变化被认为与SERT基因减少引起的行为改变相当。这两种模型都与人类高度相关，但它们在SERT破坏的时间框架上有所不同。我们发现，两种模型在焦虑相关行为以及重要的潜在血清素神经传递方面存在差异。在小鼠中，SERT的组成性缺失会导致与焦虑相关行为的终生增加以及高血清素血症。相反，早期接触抗抑郁药艾司西酞普兰（ESC；来士普）会导致从青春期开始与焦虑相关行为减少，这与成年期腹侧海马体中血清素系统功能减退有关。早期接触氟西汀（百忧解）导致的成年行为变化与ESC不同，虽然在某种程度上与SERT缺乏相似，但与成年后期海马体血清素传递的变化无关。这些发现揭示了发育过程中接触不同广泛使用的抗抑郁药所导致的成年行为和神经传递的差异，而基因SERT不足并不能重现这些差异。此外，它们支持血清素能调节在焦虑相关行为中起关键作用。
