Richtand Neil M, Taylor Benjamin, Welge Jeffrey A, Ahlbrand Rebecca, Ostrander Michelle M, Burr Jeffrey, Hayes Scott, Coolen Lique M, Pritchard Laurel M, Logue Aaron, Herman James P, McNamara Robert K
Cincinnati Veterans Affairs Medical Center, Psychiatry Service (V116A), Cincinnati, OH, USA.
Neuropsychopharmacology. 2006 Jan;31(1):77-89. doi: 10.1038/sj.npp.1300791.
Long-standing behavioral abnormalities emerge after puberty in rats following neonatal hippocampal lesion, providing a developmental model of abnormal rat behavior that may have predictive validity in identifying compounds effective in treating symptoms of schizophrenia. We sought to test the predictive validity of the neonatal hippocampal lesion model in identifying preventive treatment for first-episode psychosis. We determined the effect of risperidone, recently studied for prevention of first-episode psychosis, on the development of elevated locomotor activity following neonatal hippocampal lesions. Rat pups received hippocampal or sham lesions on postnatal day 7, followed by treatment with risperidone or vehicle from postnatal days 35 to 56. Locomotor activity in response to novelty, amphetamine, and nocturnal locomotion were determined on postnatal day 57. Low-dose risperidone (45 microg/kg) pretreatment prevented elevated locomotor activity in some, but not all, of the behavioral tasks following neonatal hippocampal lesions. In contrast, higher risperidone pretreatment was less effective in preventing elevated locomotor activity following neonatal hippocampal lesions. Because low risperidone dosages were also found to be effective in preventing first-episode psychosis in human studies, these data support the predictive validity of the hippocampal lesion model in identifying medications for prevention of first-episode psychosis. Additionally, these data support the use of low-dose risperidone in psychosis prevention, and suggest the possibility that higher risperidone doses could be less effective in this application.
新生大鼠海马损伤后，青春期会出现长期行为异常，这为异常大鼠行为提供了一种发育模型，该模型在识别有效治疗精神分裂症症状的化合物方面可能具有预测效度。我们试图测试新生海马损伤模型在识别首发精神病预防性治疗方面的预测效度。我们确定了最近用于预防首发精神病研究的利培酮对新生海马损伤后运动活动增加的发育的影响。幼鼠在出生后第7天接受海马损伤或假手术，然后在出生后第35天至56天用利培酮或赋形剂治疗。在出生后第57天测定对新奇刺激、安非他明的反应性运动活动以及夜间运动活动。低剂量利培酮（45微克/千克）预处理可预防新生海马损伤后部分但并非所有行为任务中的运动活动增加。相比之下，较高剂量利培酮预处理在预防新生海马损伤后运动活动增加方面效果较差。由于在人体研究中也发现低剂量利培酮对预防首发精神病有效，这些数据支持海马损伤模型在识别预防首发精神病药物方面的预测效度。此外，这些数据支持使用低剂量利培酮预防精神病，并表明较高剂量利培酮在该应用中可能效果较差。
