Neonatal ventral hippocampal-lesioned (NVHL) rats have been shown to display neurochemical and behavioral abnormalities at adulthood, analogous to some of those seen in schizophrenia. Serotonergic neurotransmission is implicated the pathophysiology and treatment of schizophrenia. In this study, we evaluated possible role of serotonergic transmission is the behaviors of NVHL-lesioned rats. Bilateral lesions to the ventral hippocampus (VH) in rat pups were made using the excitotoxin ibotenic acid. We investigated 5-HT2A-receptor and SERT binding sites in cortical and subcortical areas in post-pubertal NVHL and sham-lesioned rats, using quantitative receptor autoradiography. We compared a 5-HT-dependent behavior in NVHL and sham animals, the wet-dog shake response (WDSr) to a 5-HT2A receptor agonist DOI. In addition, we studied prepulse inhibition (PPI) of startle responses in NVHL and Sham-lesioned animals treated with antipsychotic drugs haloperidol, risperidone and clozapine and 5-HT2A antagonists ketanserin or MDL100907. The WDSr elicited by DOI was enhanced in post-pubertal NVHL rats compared to sham-lesioned controls. Moreover, post-pubertal NVHL rats exhibited PPI deficits which was reversed by atypical antipsychotics, ketanserin and MDL100907. A significant increase in 5-HT2A-like receptor binding was observed in the medial prefrontal cortex (mPFC) in post-pubertal NVHL rats without any significant change in the striatum and ventral pallidum. A significant increase in SERT-like binding was also observed in the mPFC and striatum of NVHL rats at pre-pubertal period; however, at post-pubertal age, the binding remained elevated in mPFC only. These data suggest that increased prefrontal cortical 5-HT transmission may play a role in the behavioral deficits observed in this neurodevelopmental model of schizophrenia.（新生仔腹側海馬傷害（NVHL）ラットは成人期に統合失調症患者にみられる神経化学的異常および行動異常を示す。セロトニン作動性神経伝達は、統合失調症の病態生理と治療に関係するとされる。本研究ではNVHLラットの行動評価を行いセロトニン作動性伝達の役割について検討したところ、統合失調症のこの神経発達モデルで観察される行動障害において、前頭前皮質の5-HT伝達の増加が役割を果たす可能性があることが示唆された。）
377:112226
Mitazaki S, Nakagawasai O, Onogi H, Watanabe K, Takahashi K, Tan-No K, Quirion R, Srivastava LK, Tadano T.
