King Madeleine V, Seeman Philip, Marsden Charles A, Fone Kevin C F
Institute of Neuroscience, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
Synapse. 2009 Jun;63(6):476-83. doi: 10.1002/syn.20624.
Postweaning social isolation in the rat induces lasting alterations that parallel several of the core symptoms seen in human schizophrenics, including hyperreactivity to novel environments, cognitive impairment, and deficits in sensorimotor gating. The current study determined whether these changes are accompanied by any elevation in the proportion of striatal dopamine receptors in the functional high affinity state (D(2) (High)), as observed in other preclinical models of psychosis. Male Lister hooded rats (20-24 days) were housed in groups of three or alone. On Day 36 postweaning locomotor activity was monitored for 60 min in a novel arena, and on Day 37 novel object discrimination was assessed using a 2 h intertrial interval. Three days later striata were collected, homogenized, washed three times to remove endogenous dopamine, and the proportion of D(2) (High) determined by competition between dopamine and 2.27 nM [(3)H]domperidone. Isolates were significantly more active than group housed controls for both ambulation and rears. Although both groups exhibited comparable levels of familiarization trial object exploration, group housed animals were able to discriminate between novel and familiar objects during the choice trial while isolates were not. Social isolation was associated with a highly significant elevation in the proportion of striatal D(2) (High), equivalent to a 3.3-fold increase (group 15.2% +/- 1.4%, isolate 49.8% +/- 4.8%; P < 0.0001, Student's unpaired t-test). These findings support both the hypothesis that elevated D(2) (High) is a common feature of multiple animal models of psychosis, and the validity of isolation rearing as a neurodevelopmental model of a "schizophrenia-like" state.
大鼠断奶后社会隔离会引发持久的改变，这些改变与人类精神分裂症患者的一些核心症状相似，包括对新环境反应过度、认知障碍以及感觉运动门控缺陷。当前研究确定这些变化是否伴随着纹状体多巴胺受体处于功能性高亲和力状态（D(2)(High)）的比例升高，正如在其他精神病临床前模型中所观察到的那样。雄性利斯特戴帽大鼠（20 - 24日龄）被分成三只一组饲养或单独饲养。在断奶后第36天，在一个新的场地监测其运动活动60分钟，在第37天，使用2小时的试验间隔评估新物体辨别能力。三天后收集纹状体，匀浆，洗涤三次以去除内源性多巴胺，并通过多巴胺与2.27 nM [(3)H]多潘立酮之间的竞争来确定D(2)(High)的比例。隔离饲养的大鼠在行走和站立方面明显比群居对照组更活跃。虽然两组在熟悉试验物体探索方面表现出相当的水平，但群居动物在选择试验中能够区分新物体和熟悉物体，而隔离饲养的大鼠则不能。社会隔离与纹状体D(2)(High)比例的高度显著升高有关，相当于增加了3.3倍（对照组15.2% +/- 1.4%，隔离组49.8% +/- 4.8%；P < 0.0001，学生非配对t检验）。这些发现既支持了D(2)(High)升高是多种精神病动物模型共同特征的假设，也支持了隔离饲养作为“精神分裂症样”状态神经发育模型的有效性。
