Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
Neurobiol Dis. 2010 Jul;39(1):116-25. doi: 10.1016/j.nbd.2010.02.001. Epub 2010 Feb 11.
The incidence of psychosis is increased in people with epilepsy, including idiopathic generalized epilepsies. To study the biological basis for this co-morbidity, we compared GAERS, a genetic rat model of absence epilepsy, to non-epileptic control rats (NEC). Mature, 14-week old GAERS showed enhanced amphetamine-induced locomotor hyperactivity - a feature also present in young (6-week old) GAERS prior to epilepsy onset. Prepulse inhibition and its disruption by psychotropic drugs did not differ between strains, although GAERS displayed elevated startle responses at both epileptic and pre-epileptic ages. The frontoparietal cortex of GAERS displayed a twofold increase in the power of gamma (30-80 Hz) oscillations, a proposed neurophysiological correlate of psychosis. Radioligand binding autoradiography demonstrated reduced densities of dopamine transporters in the caudate nucleus and nucleus accumbens core and of dopamine D2 receptors in the caudate nucleus. GAERS provide an opportunity to study the neurodevelopmental, genetic and therapeutic aspects of psychiatric comorbidities associated with epilepsy.
癫痫患者的精神病发病率增加，包括特发性全面性癫痫。为了研究这种合并症的生物学基础，我们比较了 GAERS，一种失神癫痫的遗传大鼠模型，与非癫痫对照大鼠（NEC）。成熟的 14 周龄 GAERS 表现出增强的安非他命诱导的运动过度兴奋——这一特征也存在于癫痫发作前的年轻（6 周龄）GAERS 中。预脉冲抑制及其被精神药物破坏在两种品系之间没有差异，尽管 GAERS 在癫痫和癫痫前年龄都表现出更高的惊跳反应。GAERS 的额顶叶皮层显示出伽马（30-80 Hz）振荡的功率增加了两倍，这是一种精神病的神经生理学相关物。放射性配体结合放射自显影显示尾状核和伏隔核核心中的多巴胺转运体密度降低，尾状核中的多巴胺 D2 受体密度降低。GAERS 为研究与癫痫相关的精神共病的神经发育、遗传和治疗方面提供了机会。
