Fradley Rosa L, O'Meara Gillian F, Newman Richard J, Andrieux Annie, Job Didier, Reynolds David S
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK.
Behav Brain Res. 2005 Sep 8;163(2):257-64. doi: 10.1016/j.bbr.2005.05.012.
Schizophrenia is a chronic and debilitating disease which is thought to arise from a neuro-developmental disorder. Both the stable tubule-only polypeptide (STOP) protein and the N-methyl-D-aspartate (NMDA) NR1 subunit are involved in neuronal development and physiology. It has therefore been postulated that transgenic mice lacking either the STOP or the NMDAR1 gene would show a 'schizophrenic-like' phenotype. Here, STOP knockout and NMDA NR1 hypomorphic mice were assessed in a behavioural measure that can be used to detect schizophrenic-like phenotypes: a change in sensorimotor gating, measured through prepulse inhibition (PPI). STOP knockout mice were further assessed in another measure of 'schizophrenic-like behaviour': hyperlocomotion. The PPI deficit exhibited by both the STOP knockout and NMDA knockdown mice could not be reversed by acute treatment with the atyptical antipsychotic, clozapine (1 mg/kg, i.p.) but the hyperlocomotion shown by the STOP knockout mice was reversed with the same acute dose of clozapine.
精神分裂症是一种慢性致残性疾病，被认为源于神经发育障碍。仅稳定小管多肽（STOP）蛋白和N-甲基-D-天冬氨酸（NMDA）NR1亚基都参与神经元发育和生理功能。因此，有人推测缺乏STOP或NMDAR1基因的转基因小鼠会表现出“精神分裂症样”表型。在此，对STOP基因敲除小鼠和NMDA NR1低表达小鼠进行了一项行为测量评估，该测量可用于检测精神分裂症样表型：通过前脉冲抑制（PPI）测量感觉运动门控的变化。对STOP基因敲除小鼠还进行了另一项“精神分裂症样行为”测量评估：运动亢进。STOP基因敲除小鼠和NMDA基因敲低小鼠表现出的PPI缺陷不能通过非典型抗精神病药物氯氮平（1mg/kg，腹腔注射）急性治疗得到逆转，但STOP基因敲除小鼠表现出的运动亢进在相同急性剂量氯氮平治疗下得到了逆转。
