Bourke Chase H, Glasper Erica R, Neigh Gretchen N
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
Department of Psychology, University of Maryland, College Park, MD, USA.
Behav Brain Res. 2014 Aug 15;270:295-9. doi: 10.1016/j.bbr.2014.05.035. Epub 2014 May 24.
Depression and anxiety during adolescence are complex disorders due to persistent effects on physiology and behavior. Selective-serotonin reuptake inhibitors (SSRI) are currently the most widely used pharmacological intervention for depression. Corticotropin-releasing factor one (CRF1) receptor antagonists represent a novel class of compounds that may have efficacy for depressive and anxiety disorders. This study used an animal model of chronic adolescent stress to determine the efficacy of the SSRI fluoxetine, and a novel CRF1 receptor antagonist, GSK876008, on prevention of the behavioral effects of chronic adolescent stress. Male rats were exposed to chronic social defeat stress, fluoxetine, and/or GSK876008 from postnatal day 28-50. Chronic stress-induced depressive-like behaviors were partially attenuated by either concurrent fluoxetine or GSK876008. Fluoxetine blunted body mass gain in the adolescents exposed to chronic stress. The collective data demonstrate similar efficacy between a SSRI and a CRF1 receptor antagonist in the attenuation of stress-induced anhedonia but fewer side effects were observed in those rats treated with the CRF1 receptor antagonist. These data suggest that CRF1 receptor antagonists may be a viable alternative for treatment of depressive behaviors in adolescents.
青少年期的抑郁和焦虑是复杂的病症，因其对生理和行为有持续影响。选择性5-羟色胺再摄取抑制剂（SSRI）是目前治疗抑郁症最广泛使用的药物干预手段。促肾上腺皮质激素释放因子1（CRF1）受体拮抗剂是一类新型化合物，可能对抑郁和焦虑症有效。本研究使用慢性青少年应激动物模型来确定SSRI氟西汀和新型CRF1受体拮抗剂GSK876008对预防慢性青少年应激行为影响的效果。雄性大鼠在出生后第28至50天暴露于慢性社会挫败应激、氟西汀和/或GSK876008。同时使用氟西汀或GSK876008可部分减轻慢性应激诱导的抑郁样行为。氟西汀使暴露于慢性应激的青少年体重增加变缓。总体数据表明，SSRI和CRF1受体拮抗剂在减轻应激诱导的快感缺失方面疗效相似，但在用CRF1受体拮抗剂治疗的大鼠中观察到的副作用较少。这些数据表明，CRF1受体拮抗剂可能是治疗青少年抑郁行为的一种可行替代方法。
