Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Neuropharmacology. 2012 Jun;62(7):2337-45. doi: 10.1016/j.neuropharm.2012.02.001. Epub 2012 Feb 15.
Previous work has indicated an association between seizures early in life and increased risk of psychiatric disorders, including schizophrenia. However, because early-life seizures are commonly treated with antiepileptic drugs (AEDs) such as phenobarbital, the possibility that drug treatment may affect later-life psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis that phenobarbital exposure in the neonatal rat increases the risk of schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we examined the effects of a single acute neonatal exposure to phenobarbital on adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion model of schizophrenia. We compared these outcomes to those in rats a) without nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition task. We found that neonatal phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced the locomotor response to amphetamine in adult animals with and without nVH lesions. Our findings suggest that neonatal exposure to phenobarbital can predispose to schizophrenia-like behavioral abnormalities. Our findings underscore the importance of examining AED exposure early in life as a potential risk factor for later-life neuropsychiatric abnormalities in clinical populations.
先前的研究表明，生命早期的癫痫发作与精神障碍（包括精神分裂症）的风险增加有关。然而，由于生命早期的癫痫发作通常用抗癫痫药物（AEDs）治疗，例如苯巴比妥，因此需要评估药物治疗是否会影响以后的精神结局。因此，我们测试了这样一个假设，即在新生大鼠中暴露于苯巴比妥会增加成年后类似精神分裂症的行为异常的风险。因此，在这项研究中，我们研究了单次急性新生大鼠暴露于苯巴比妥对成年大鼠海马腹侧海马（nVH）损伤精神分裂症模型中行为结果的影响。我们将这些结果与未进行 nVH 损伤的大鼠 a）和未进行苯巴比妥治疗的大鼠 b）进行了比较。用于行为评估的任务包括：安非他命诱导的运动、预脉冲抑制、高架十字迷宫和新颖物体识别任务。我们发现，新生大鼠苯巴比妥治疗（无 nVH 损伤）足以破坏成年大鼠的感觉运动门控（如预脉冲抑制测试），其程度与 nVH 损伤相当。此外，新生大鼠苯巴比妥暴露增强了成年动物（无论是否有 nVH 损伤）对安非他命的运动反应。我们的研究结果表明，新生大鼠暴露于苯巴比妥会导致类似精神分裂症的行为异常。我们的研究结果强调了在临床人群中，检查生命早期的 AED 暴露作为以后发生神经精神异常的潜在危险因素的重要性。
