Health Innovations Research Institute and School of Medical Sciences, RMIT University, Bundoora, Victoria 3083, Australia.
Neurosci Lett. 2010 Mar 8;471(3):144-7. doi: 10.1016/j.neulet.2010.01.028. Epub 2010 Jan 25.
Persistent blockade of NMDA receptor function by repeated phencyclidine dosing produces pathophysiological changes that model deficits observed in schizophrenia. The present study investigates the effects of subchronic phencyclidine administration (PCP; 2 or 5mg/kg bi-daily for 7 days followed by a drug-free period) on sucrose choice, a measure of anhedonia. Sucrose preference in a two-bottle sucrose-water choice test was assessed 1 and 2 weeks after PCP. Results showed no differences in sucrose intake between PCP rats and controls, nor a difference in water intake or total volume of liquid consumed at either time-point. Six weeks post-PCP, analysis of brains showed a reduction in expression of parvalbumin immunoreactive neurons in the hippocampus with significant reductions localised to the CA1 and CA2/3 regions. These results demonstrate that while subchronic PCP may not be a valid model for the negative symptom of anhedonia observed in schizophrenia, it induces pathology in the brain in hippocampal subregions that are reminiscent of changes observed in schizophrenia.
反复给予苯环己哌啶(PCP)可导致 NMDA 受体功能持续阻断,从而产生模拟精神分裂症中观察到的缺陷的病理生理变化。本研究调查了亚慢性 PCP 给药(PCP;2 或 5mg/kg 每日两次,共 7 天,然后无药物期)对蔗糖选择的影响,蔗糖选择是快感缺失的一种衡量标准。在 PCP 后 1 周和 2 周,通过双瓶蔗糖水选择测试评估蔗糖偏好。结果显示,PCP 大鼠与对照组之间的蔗糖摄入量没有差异,在任何时间点,水摄入量或总液体摄入量也没有差异。PCP 后 6 周,对大脑的分析显示海马 CA1 和 CA2/3 区域 PARVALBUMIN 免疫反应性神经元的表达减少,这些区域的减少与精神分裂症中观察到的变化相似。这些结果表明,虽然亚慢性 PCP 可能不是精神分裂症中观察到的快感缺失阴性症状的有效模型,但它会引起海马亚区的脑病理学变化,这些变化与精神分裂症中观察到的变化相似。