Marks Wendie N, Cavanagh Mary E, Greba Quentin, Cain Stuart M, Snutch Terrance P, Howland John G
Department of Physiology, University of Saskatchewan, GB33, Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, Canada, S7N 5E5.
Michael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
Eur J Neurosci. 2016 Jan;43(1):25-40. doi: 10.1111/ejn.13110. Epub 2015 Nov 25.
Behavioural, neurological, and genetic similarities exist in epilepsies, their psychiatric comorbidities, and various psychiatric illnesses, suggesting common aetiological factors. Rodent models of epilepsy are used to characterize the comorbid symptoms apparent in epilepsy and their neurobiological mechanisms. The present study was designed to assess Pavlovian fear conditioning and latent inhibition in a polygenetic rat model of absence epilepsy, i.e. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and the non-epileptic control (NEC) strain. Electrophysiological recordings confirmed the presence of spike-wave discharges in young adult GAERS but not NEC rats. A series of behavioural tests designed to assess anxiety-like behaviour (elevated plus maze, open field, acoustic startle response) and cognition (Pavlovian conditioning and latent inhibition) was subsequently conducted on male and female offspring. Results showed that GAERS exhibited significantly higher anxiety-like behaviour, a characteristic reported previously. In addition, using two protocols that differed in shock intensity, we found that both sexes of GAERS displayed exaggerated cued and contextual Pavlovian fear conditioning and impaired fear extinction. Fear reinstatement to the conditioned stimuli following unsignalled footshocks did not differ between the strains. Male GAERS also showed impaired latent inhibition in a paradigm using Pavlovian fear conditioning, suggesting that they may have altered attention, particularly related to previously irrelevant stimuli in the environment. Neither the female GAERS nor NEC rats showed evidence of latent inhibition in our paradigm. Together, the results suggest that GAERS may be a particularly useful model for assessing therapeutics designed to improve the emotional and cognitive disturbances associated with absence epilepsy.
癫痫、其精神共病以及各种精神疾病在行为、神经学和遗传学方面存在相似性,这表明存在共同的病因因素。癫痫的啮齿动物模型用于表征癫痫中明显的共病症状及其神经生物学机制。本研究旨在评估斯特拉斯堡遗传性失神癫痫大鼠(GAERS)这一失神癫痫多基因大鼠模型以及非癫痫对照(NEC)品系中的巴甫洛夫恐惧条件反射和潜伏抑制。电生理记录证实年轻成年GAERS大鼠存在棘波放电,而NEC大鼠则没有。随后对雄性和雌性后代进行了一系列旨在评估焦虑样行为(高架十字迷宫、旷场、听觉惊吓反应)和认知(巴甫洛夫条件反射和潜伏抑制)的行为测试。结果表明,GAERS表现出显著更高的焦虑样行为,这是先前报道过的一个特征。此外,使用两种电击强度不同的方案,我们发现GAERS的雌雄两性都表现出夸张的线索性和情境性巴甫洛夫恐惧条件反射以及恐惧消退受损。在无信号足部电击后,对条件刺激的恐惧恢复在两个品系之间没有差异。雄性GAERS在使用巴甫洛夫恐惧条件反射的范式中也表现出潜伏抑制受损,这表明它们可能改变了注意力,特别是与环境中先前无关的刺激有关。在我们的范式中,雌性GAERS和NEC大鼠均未表现出潜伏抑制的证据。总之,结果表明GAERS可能是一种特别有用的模型,用于评估旨在改善与失神癫痫相关的情绪和认知障碍的治疗方法。