Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Trends Pharmacol Sci. 2011 Sep;32(9):507-13. doi: 10.1016/j.tips.2011.05.001. Epub 2011 Jun 21.
Substantial evidence suggests that psychosis in schizophrenia is associated with dysregulation of subcortical dopamine system function. Here we examine evidence that this dysregulation is secondary to hyperactivity within hippocampal subfields. Enhanced hippocampal activity has been reported in preclinical models and in schizophrenia patients. Moreover, this hippocampal hyperactivity is correlated with enhanced dopamine neuron activity and positive symptoms, respectively. Thus, restoration of hippocampal function could provide a more effective therapeutic approach than current therapeutics based on blockade of dopamine D2 receptors. Indeed, initial studies demonstrate that allosteric modulation of the α5GABA(A) receptor can decrease aberrant dopamine signaling and associated behaviors in a verified rodent model of psychosis.
大量证据表明，精神分裂症中的精神病与皮质下多巴胺系统功能失调有关。在这里，我们研究了这种失调是否是海马亚区过度活跃的结果。在临床前模型和精神分裂症患者中都有报道称，海马活动增强。此外，这种海马活动过度与多巴胺神经元活动增强和阳性症状分别相关。因此，恢复海马功能可能提供比基于多巴胺 D2 受体阻断的当前治疗方法更有效的治疗方法。事实上，初步研究表明，α5GABA(A)受体的变构调节可以减少验证性精神分裂症动物模型中的异常多巴胺信号和相关行为。
