Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Neuropsychopharmacology. 2013 Sep;38(10):1881-8. doi: 10.1038/npp.2013.101. Epub 2013 Apr 23.
Schizophrenia is believed to arise from an interaction of genetic predisposition and adverse environmental factors, with stress being a primary variable. We propose that alleviating anxiety produced in response to stress during a sensitive developmental period may circumvent the dopamine (DA) system alterations that may correspond to psychosis in adults. This was tested in a developmental rat model of schizophrenia based on prenatal administration of the mitotoxin methyl azoxymethanol acetate (MAM). MAM administration leads to a hyperdopaminergic state consisting of an increase in the number of DA neurons firing spontaneously, which correlates with an increased behavioral response to amphetamine. MAM-treated rats exhibited a heightened level of anxiety during adolescence. Peripubertal administration of the antianxiety agent diazepam was found to prevent the increase in DA neuron activity and blunt the behavioral hyperresponsivity to amphetamine in these rats. These data suggest that the pathophysiological factors leading to the onset of psychosis in early adulthood may be circumvented by controlling the response to stress during the peripubertal period.
精神分裂症被认为是遗传易感性和不利环境因素相互作用的结果，其中压力是一个主要变量。我们提出，在敏感的发育阶段缓解应激引起的焦虑，可能会避免与成人精神病相对应的多巴胺（DA）系统改变。这在基于产前给予促有丝分裂原甲基偶氮甲烷乙酸盐（MAM）的精神分裂症发育大鼠模型中进行了测试。MAM 给药导致多巴胺能亢进状态，表现为自发放电的 DA 神经元数量增加，这与对安非他命的行为反应增加相关。MAM 处理的大鼠在青春期表现出更高水平的焦虑。研究发现，青春期前给予抗焦虑药地西泮可预防 DA 神经元活动的增加，并减轻这些大鼠对安非他命的行为高反应性。这些数据表明，通过控制青春期期间对压力的反应，可能会避免导致成年早期精神病发作的病理生理因素。
