Tseng Kuei Y, Chambers R Andrew, Lipska Barbara K
Department of Cellular & Molecular Pharmacology, RFUMS/The Chicago Medical School, North Chicago, IL 60064, USA.
Behav Brain Res. 2009 Dec 7;204(2):295-305. doi: 10.1016/j.bbr.2008.11.039. Epub 2008 Dec 3.
Traditionally, animal models of schizophrenia were predominantly pharmacological constructs focused on phenomena linked to dopamine and glutamate neurotransmitter systems, and were created by direct perturbations of these systems. A number of developmental models were subsequently generated that allowed testing of hypotheses about the origin of the disease, mimicked a wider array of clinical and neurobiological features of schizophrenia, and opened new avenues for developing novel treatment strategies. The most thoroughly characterized (approximately 100 primary research articles) is the neonatal ventral hippocampal lesion (NVHL) model, which is the subject of this review. We highlight its advantages and limitations, and how it may offer clues about the extent to which positive, negative, cognitive, and other aspects of schizophrenia, including addiction vulnerability, represent inter-related pathophysiological mechanisms.
传统上,精神分裂症的动物模型主要是药理学构建物,聚焦于与多巴胺和谷氨酸神经递质系统相关的现象,并通过对这些系统的直接干扰来创建。随后产生了一些发育模型,这些模型能够对有关该疾病起源的假说进行测试,模拟了精神分裂症更广泛的临床和神经生物学特征,并为开发新的治疗策略开辟了新途径。特征描述最为详尽的(约有100篇主要研究文章)是新生大鼠腹侧海马损伤(NVHL)模型,它也是本综述的主题。我们将强调其优点和局限性,以及它如何为精神分裂症的阳性、阴性、认知及其他方面(包括成瘾易感性)在多大程度上代表相互关联的病理生理机制提供线索。