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Keywords:

  • animal model;
  • development;
  • prefrontal cortex;
  • striatum;
  • TBPS;
  • schizophrenia

Abstract

Rats with neonatal ventral hippocampal lesions (NVHL) have been studied as a neurodevelopmental animal model of schizophrenia. NVHL rats exhibit postpubertal emergence of hyperresponsiveness to stress, suggesting increased mesolimbic dopamine (DA) activity. However, previous studies have not yielded clear evidence of this. Disturbances in the γ-amino-butyric acid (GABA)-ergic system as well as the dopaminergic system are thought to be present in schizophrenia. To determine whether GABAA receptors play a role in the abnormal postpubertal behavior in NVHL rats, we compared changes in expression of mRNA of GABAA receptor subunits and in [35S] t-butylbicyclophosphorothionate ([35S] TBPS) binding in the prepubertal and postpubertal periods. Male pups were lesioned with ibotenic acid at postnatal day 7 (PD 7), and in situ hybridization and quantitative autoradiography were then performed. In NVHL rats, α1 subunit mRNA expression in prefrontal cortex was decreased at PD 35 (prepubertal period; by 21.7%), but increased at PD 56 (postpubertal period; by 21.4%) when compared with sham controls. β2 subunit mRNA expression was increased in PFC in the postpubertal period (by 24.3%). β3 subunit mRNA expression was increased in the caudate-putamen in the postpubertal period (by 37.2%). [35S] TBPS binding was increased in PFC only in the postpubertal period (by 17.7%). These findings suggest that dysfunction of the GABAergic system exists in NVHL rats. Furthermore, developmental and regional changes in GABAA receptor expression appear to occur in compensation for the attenuation of GABAergic system activity in NVHL rats. Synapse 61:357-366, 2007. © 2007 Wiley-Liss, Inc.