Reed Abbey L, Anderson Jeffrey C, Bylund David B, Petty Frederick, El Refaey Hesham, Happe H Kevin
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800, USA.
Psychopharmacology (Berl). 2009 Aug;205(2):249-59. doi: 10.1007/s00213-009-1535-2. Epub 2009 Apr 22.
The pharmacological treatment of depression in children and adolescents is different from that of adults due to the lack of efficacy of certain antidepressants in the pediatric age group. Our current understanding of why these differences occur is very limited.
To develop more effective treatments, a juvenile animal model of depression was tested to validate it as a possible model to specifically study pediatric depression.
Procedures for use with juvenile rats at postnatal day (PND) 21 and 28 were adapted from the adult learned helplessness model in which, 24 h after exposure to inescapable stress, animals are unable to remove themselves from an easily escapable stressor. Rats were treated for 7 days with either the selective serotonin reuptake inhibitor escitalopram at 10 mg/kg or the tricyclic antidepressant desipramine at 3, 10, or 15 mg/kg to determine if treatment could decrease escape latency times.
Escitalopram treatment was effective at decreasing escape latency times in all ages tested. Desipramine treatment did not decrease escape latency times for PND 21 rats, but did decrease times for PND 28 and adult animals.
The learned helplessness model with PND 21 rats predicts the efficacy of escitalopram and the lack of efficacy of desipramine seen in the treatment of pediatric depression. These findings suggest that the use of PND 21 rats in a modified learned helplessness procedure may be a valuable model of human pediatric depression that can predict pediatric antidepressant efficacy and be used to study antidepressant mechanisms involved in pediatric depression.
由于某些抗抑郁药在儿童和青少年年龄组中缺乏疗效，儿童和青少年抑郁症的药物治疗与成人不同。我们目前对这些差异为何会出现的理解非常有限。
为了开发更有效的治疗方法，对一种幼年动物抑郁症模型进行了测试，以验证其作为专门研究儿童抑郁症的可能模型。
针对出生后第21天和第28天的幼年大鼠的实验程序改编自成年习得性无助模型，即在暴露于不可逃避的应激24小时后，动物无法从易于逃避的应激源中解脱出来。用10mg/kg的选择性5-羟色胺再摄取抑制剂艾司西酞普兰或3、10或15mg/kg的三环类抗抑郁药地昔帕明对大鼠进行7天治疗，以确定治疗是否能缩短逃避潜伏期。
在所有测试年龄组中，艾司西酞普兰治疗均能有效缩短逃避潜伏期。地昔帕明治疗对出生后第21天的大鼠逃避潜伏期无缩短作用，但对出生后第28天的大鼠和成年动物有缩短作用。
出生后第21天大鼠的习得性无助模型可预测艾司西酞普兰在儿童抑郁症治疗中的疗效以及地昔帕明的无效性。这些发现表明，在改良的习得性无助程序中使用出生后第21天的大鼠可能是人类儿童抑郁症的一个有价值的模型，可预测儿童抗抑郁药的疗效，并用于研究儿童抑郁症中涉及的抗抑郁机制。
