Le Pen Gwenaëlle, Moreau Jean-Luc
Pharma Division, Preclinical CNS Research, F-Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland.
Neuropsychopharmacology. 2002 Jul;27(1):1-11. doi: 10.1016/S0893-133X(01)00383-9.
Neonatal ventral hippocampal (NVH) lesions in rats have been shown to induce behavioral abnormalities at adulthood thought to simulate some aspects of positive, negative and cognitive deficits classically observed in schizophrenic patients. Such lesions induced a post-pubertal emergence of prepulse inhibition deficits reminiscent of the sensorimotor gating deficits observed in a large majority of schizophrenic patients. Here we have investigated the capacity of typical and atypical antipsychotics to reverse PPI deficits seen in NVH-lesioned rats. We show that three atypical antipsychotics (clozapine, olanzapine and risperidone) were able to reverse lesion-induced PPI deficits, in contrast to haloperidol, a classical neuroleptic. These results show that the NVH lesion model seems to be endowed with a fair predictive validity as, like in schizophrenic patients, PPI deficits in lesioned animals were reversed by atypical antipsychotics but not by the typical neuroleptic haloperidol.
大鼠新生儿期腹侧海马（NVH）损伤已被证明会在成年期诱发行为异常，这些异常被认为模拟了精神分裂症患者经典观察到的阳性、阴性和认知缺陷的某些方面。此类损伤会导致青春期后出现前脉冲抑制缺陷，这让人联想到在大多数精神分裂症患者中观察到的感觉运动门控缺陷。在此，我们研究了典型和非典型抗精神病药物逆转NVH损伤大鼠中前脉冲抑制缺陷的能力。我们发现，与经典抗精神病药物氟哌啶醇不同，三种非典型抗精神病药物（氯氮平、奥氮平和利培酮）能够逆转损伤诱导的前脉冲抑制缺陷。这些结果表明，NVH损伤模型似乎具有相当的预测效度，因为与精神分裂症患者一样，损伤动物中的前脉冲抑制缺陷可被非典型抗精神病药物逆转，但不能被典型抗精神病药物氟哌啶醇逆转。
