Han Dai, Shi Shenxun, Luo Hong
Institutes of Psychological Sciences, Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, P. R. China.
Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, Zhejiang, 311121, P. R. China.
J Integr Neurosci. 2019 Sep 30;18(3):245-251. doi: 10.31083/j.jin.2019.03.186.
The cognitive impairment associated with schizophrenia is highly prevalent and affects the overall functioning of subjects. The stimulation of the serotonin 1A receptor is a primary characteristic of some atypical antipsychotic drugs. We measured the levels of cognitive impairment using the Morris water maze test and protein kinase A activity in hippocampal neurons on presynaptic and postsynaptic serotonin 1A receptors to investigate the effect of dizocilpine-induced cognitive impairment associated with atypical antipsychotic drugs in rats treated by quetiapine alone or combined with WAY100635/tandospirone. The results of the Morris water maze test presented evidence that quetiapine alone alleviated the cognitive impairment associated with atypical antipsychotic drugs induced by dizocilpine. However, quetiapine plus WAY100635 induced no improvement of cognitive impairment associated with atypical antipsychotic drugs. The results of protein kinase A assay suggested that neither quetiapine alone nor in combination with tandospirone, but not quetiapine plus WAY100635, raised protein kinase A activity in hippocampus neurons. The present study demonstrated the key role of presynaptic serotonin 1A receptors on the therapeutic effect of quetiapine on cognitive impairment associated with atypical antipsychotic drugs. Moreover, that protein kinase A activity in hippocampal cells is involved in the mechanism of quetiapine's effect on cognitive impairment associated with atypical antipsychotic drugs.
与精神分裂症相关的认知障碍非常普遍，会影响患者的整体功能。刺激5-羟色胺1A受体是一些非典型抗精神病药物的主要特征。我们使用莫里斯水迷宫试验测量认知障碍水平，并检测海马神经元突触前和突触后5-羟色胺1A受体上的蛋白激酶A活性，以研究单独使用喹硫平或联合使用WAY100635/坦度螺酮治疗的大鼠中，地佐环平诱导的与非典型抗精神病药物相关的认知障碍的影响。莫里斯水迷宫试验结果表明，单独使用喹硫平可减轻地佐环平诱导的与非典型抗精神病药物相关的认知障碍。然而，喹硫平加WAY100635并未改善与非典型抗精神病药物相关的认知障碍。蛋白激酶A检测结果表明，单独使用喹硫平或与坦度螺酮联合使用均不能提高海马神经元中的蛋白激酶A活性，但喹硫平加WAY100635则可以。本研究证明了突触前5-羟色胺1A受体在喹硫平对与非典型抗精神病药物相关的认知障碍的治疗作用中的关键作用。此外，海马细胞中的蛋白激酶A活性参与了喹硫平对与非典型抗精神病药物相关的认知障碍的作用机制。
