Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Int J Neuropsychopharmacol. 2013 Jul;16(6):1331-9. doi: 10.1017/S1461145712001344. Epub 2012 Nov 28.
Subcortical dopamine system dysregulation has been suggested to underlie the positive symptoms of schizophrenia. Recent preclinical investigations and human imaging studies have proposed that the augmented dopamine system function observed in schizophrenia patients may be secondary to aberrant hippocampal activity. Thus, we posit that the hippocampus represents a novel therapeutic target for the treatment of schizophrenia. Here we provide evidence of the effectiveness of a unique approach aimed at decreasing hippocampal function in a rodent model of schizophrenia. Specifically, in a rodent model of schizophrenia, we demonstrate that ventral hippocampal (vHipp) deep brain stimulation (DBS) can normalize aberrant dopamine neuron activity and behaviours associated with positive symptoms. In addition, we provide evidence that this approach may also be effective in restoring deficits in cognitive function, often left unaltered by conventional antipsychotic medications. Therefore, we have provided initial preclinical evidence demonstrating the feasibility of hippocampal DBS as a potential novel approach for the treatment of schizophrenia.
皮质下多巴胺系统失调被认为是精神分裂症阳性症状的基础。最近的临床前研究和人类影像学研究表明,精神分裂症患者中观察到的多巴胺系统功能增强可能是海马活动异常的结果。因此,我们假设海马代表了治疗精神分裂症的一个新的治疗靶点。在这里,我们提供了一种针对精神分裂症啮齿动物模型中降低海马功能的独特方法的有效性证据。具体来说,在精神分裂症的啮齿动物模型中,我们证明腹侧海马(vHipp)深部脑刺激(DBS)可以使异常的多巴胺神经元活动和与阳性症状相关的行为正常化。此外,我们还提供了证据表明,这种方法也可能有效地恢复认知功能的缺陷,而这些缺陷通常不会被传统的抗精神病药物改变。因此,我们已经提供了初步的临床前证据,证明了海马 DBS 作为治疗精神分裂症的一种潜在新方法的可行性。