目的 探讨青春期前大鼠精神分裂症的多巴胺机制,为精神分裂症的早期预防及诊断提供重要依据。方法 母鼠孕期17 d时腹腔注射甲基氧化偶氮甲醇醋酸盐(methylazoxymethanol acetate,MAM)/盐水(25 mg/kg),选取出生后35~40 d龄的雄性子鼠作为模型实验动物,出生后10周作为成年动物。实验一:随机分为青春期前模型组和对照组,成年模型组和对照组,每组10只动物,于腹侧海马埋置刺激电极,通过自由运动行为法检测各组动物在接受阿朴吗啡刺激和腹侧海马电刺激后的行为变化;实验二:另有正常或MAM处理后的青春期前和成年大鼠各10只,记录腹侧被盖区(VTA)多巴胺能神经元放电活动,并于腹侧海马(vHipp)注射盐水/MK801,观察自发放电的变化。结果 细胞外记录实验发现, MAM处理大鼠的子代VTA自发放电的多巴胺能神经元数目明显增多,且被vHipp注射MK801所翻转。成年精神分裂模型大鼠基础活动明显增加,对vHipp刺激后阿朴吗啡的刺激反应也明显增强;而青春期前和精神分裂模型组大鼠对vHipp电刺及对阿朴吗啡的刺激均无明显反应。结论 精神分裂症大鼠的病理生理学改变在青春期前已经出现,但并未引发行为异常,青春期是多巴胺受体功能改变的关键期。
Abstract
Objective To discuss the relationship of aberrant regulation of dopamine system function and schizophrenia.Methods Pregnant female Sprague Dawley rats were obtained at MAM (methylazoxymethanol acetate,diluted in saline,25mg/kg,i.p.) or saline was administered on GD17.Post-weaning,pre-adolescent rats were defined as postnatal day 35~40,whereas adult rats were over 10 weeks of age.Test 1:normal pre-adolescent rats and MAM-treated pre-adolescent rats;Adult normal rats and adult MAM-treated rats were implanted electrodes into ventral hippocampus (vHipp) to exam the effect of electric stimuli and apomorphine on locomotor activity of rats.Test 2:The spontaneous firing activity of dopamine neurons in VTA was recorded with normal or MAM-treated pre-adolescent rats,and the effect of MK-801 was observed on the dopamine neurons' firing activity. Results MAM-treated rats displayed a significant increase in the number of spontaneously active dopamine neurons throughout the VTA without significant changes in firing rate or burst firing,which could be withdraw by MK-801 injecting intra-vHipp.Adult MAM-treated rats presented an increase locomotor activity,and electric stimulation in vHipp Results in an augmented locomotor were responsed to amphetamine administration followed.However,these behavioral changes did not happen on the pre-adolescent normal or MAM-treated rats.Conclusion s The pathophysiological changes of schizophrenia have already happened in pre-adolescent period,which do not Results the abnormal behavior activity till adult.Puberty is onset of dopamine receptors' functional changes.Therefore,pre-adolescent is a critical period for Prevention and screening of schizophrenia.
关键词
精神分裂症 /
腹侧海马 /
多巴胺能神经元
Key words
schizophrenia /
ventral hippocampus /
dopamine neuron
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参考文献
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基金
国家自然科学基金青年项目(81100238);中国博士后科学基金(2014M550500)
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