Laboratory of Developmental Psychopharmacology, Department of Psychiatry, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Dev Neurosci. 2012;34(2-3):210-7. doi: 10.1159/000339162. Epub 2012 Jul 6.
Exposure to adversity during development is an identified risk factor for depression later in life. In humans, early adversity accelerates the onset of depressive symptoms, which manifest during adolescence. Animal studies have used maternal separation as a model of early adversity to produce adult depressive-like behaviors, but have yet to examine these behaviors during adolescence. Moreover, the nature of depressive-like behaviors has not been well characterized in this model. Here, we used the triadic model of learned helplessness to understand controllability, helplessness, and motivational factors following maternal separation in male and female adolescent rats. We found sex-dependent changes in the effects of separation, with males demonstrating loss of controllability in an escapable shock condition, whereas females demonstrated motivational impairment in a no-shock condition. The effect, however, did not endure as adult females were no longer helpless. Reductions in parvalbumin, a GABAergic marker, in the prefrontal cortex of separated subjects relative to age-matched controls were evident and paralleled depressive-like behavior. Understanding the risk factors for depression, the nature of depressive-like behaviors, and their unique sex dependency may ultimately provide insight into improved treatments.
在发展过程中遭遇逆境是导致日后抑郁的一个已知风险因素。在人类中，早期逆境会加速抑郁症状的出现，这些症状在青春期表现出来。动物研究已经使用母体分离作为早期逆境的模型来产生成年抑郁样行为，但尚未在青春期检查这些行为。此外，在该模型中，抑郁样行为的性质尚未得到很好的描述。在这里，我们使用习得性无助的三元模型来理解雄性和雌性青春期大鼠在母体分离后的可控制性、无助性和动机因素。我们发现分离的影响存在性别依赖性，雄性在可逃避的电击条件下表现出可控制性丧失，而雌性在无电击条件下表现出动机障碍。然而，这种影响并没有持续下去，因为成年雌性不再无助。与年龄匹配的对照组相比，分离组的前额叶皮层中 GABA 能标志物 parvalbumin 减少，这与抑郁样行为相对应。了解抑郁的风险因素、抑郁样行为的性质及其独特的性别依赖性，最终可能为改善治疗提供启示。
