Prepulse inhibition and prevertion of disease in a putative animal model of schizophrenia

前脉冲抑制（PPI）缺陷已被证明在大鼠通过神经解剖或环境操纵。本研究的目的是确定是否单侧内嗅皮层（EC）病变和/或隔离住房的影响声惊吓在青春期大鼠的PPI。我们还研究了氟哌啶醇或氯氮平对EC损伤大鼠PPI破坏的急性影响。将喹啉酸（损伤手术）或磷酸盐缓冲盐水（假手术）注入青春期（出生后7周）雄性Wistar大鼠的单侧EC。手术后，将大鼠单独饲养或成对饲养，从而产生损伤/隔离、损伤/配对、假手术/隔离和假手术/配对组。术后第28天，单侧毁损组大鼠PPI较假手术组明显减弱。此外，与左侧损伤/配对大鼠相比，左侧损伤/隔离大鼠的PPI显著降低， ...更多信息 而右侧毁损组则无此隔离效应。氟哌啶醇和氯氮平都能逆转左或右EC损伤大鼠PPI的破坏。这些研究结果表明，左EC病变可能会增强环境应激的能力，产生干扰的感觉运动门控，并在EC病变大鼠的PPI中断可能依赖于改变多巴胺（DA）的传输。此外，我们测量了DA相关的行为和甲基苯丙胺（MAP）诱导的DA释放的中脑（NAC）核在这些动物。损伤大鼠的自发或MAP（1 mg/kg，i. p.）术后第14天和第28天诱导自发活动。术后第28天，用体内微透析法测定MAP诱导的NAC DA释放。与假手术动物相比，损伤大鼠在NAC中MAP诱导的DA释放没有显着变化。这些结果表明，兴奋性毒性损伤的左EC产生的行为变化与改变mesolimbic多巴胺能传递，可能介导的突触后替代性。精氨酸加压素（AVP）是一种参与啮齿动物社会行为的肽。为探讨阻断N-甲基-D-天冬氨酸（NMDA）受体引起的社会行为障碍的机制，本研究观察了PCP对AVP受体结合和社会交往的影响。亚慢性PCP给药（2 mg/kg/天，14天，i. p.）显著降低了几个脑区中由[125 i]-线性AVP拮抗剂标记的V1 a受体结合位点的密度。如先前报告所述，五氯苯酚的亚慢性治疗损害了大鼠的社会互动。这些结果表明，NMDA受体拮抗剂对中枢加压素系统和社会互动具有调节作用。少

Prepulse inhibition(PPI) deficits have been shown in rats through neuroanatomical or environmental manipulation. The aim of this study was to determine whether unilateral entorhinal cortical(EC) lesions and/or isolation-housing influence the PPI of acoustic startle in adolescent rats. We also investigated the acute effects of haloperidol or clozapine on the disruption of PPI in the EC lesioned rats. Quinolinic acid (lesion operation) or phosphate buffered saline (sham operation) was infused into the unilateral EC of adolescent (postnatal 7 weeks) male Wistar rats. After operation, the rats were housed individually or pair-housed, thus yielding lesion/isolation, lesion/pair, sham/isolation, and sham/pair groups. On the 28th postoperative day, the rats with the unilateral lesions exhibited attenuation of PPI compared with that of the sham-operated rats. Moreover, the left lesion/isolation rats demonstrated a significantly greater decrease in PPI compared with the left lesion/pair rats, w … More hile this effect of isolation was not found in the right-lesioned rats. Both haloperidol and clozapine reversed the disruption of PPI in the left or right EC lesioned rats. These findings suggest that left EC lesions may enhance the ability of environmental stress to produce disturbances in sensorimotor gating, and that the disruption of PPI in EC lesioned rats may be dependent on altered dopamine (DA) transmissions. Furthermore, we measured DA-related behaviors and methamphetamine (MAP)-induced DA release in the accumbens (NAC) nucleus in these animals. The lesioned rats exhibited significantly greater spontaneous or MAP (1mg/kg, i.p.)-induced locomotor activity on the 14th and 28th postoperative day. MAP-induced DA release in NAC was measured by in vivo microdialysis on the 28th postoperative day. Lesioned rats did not show a significant change in MAP-induced DA release in NAC compared to sham-operated animals. These results suggest that excitotoxic damage of the left EC produces behavioral changes consistent with alterd mesolimbic dopaminergic transmissions, possibly mediated by postsynaptic supersesitivity.Animals treated with phencyclidine (PCP) are thought animal models of schizophrenia. Arginine vasopressin(AVP) is a peptide involved in social behaviors in rodents. To iinvestigate the mechanism underlying the deficits in social behavior induced by blockade of N-methyl-D-aspartate (NMDA) receptors, this study examined the effect of PCP on AVP receptor binding and social interaction in the rats. Subchronic PCP administration (2mg/kg/day, 14 days, i.p.) significantly reduced the density of V1a reveptor binding sites, labeled by an [125i]-linear AVP antagonist, in several brain regions. Subchronic treatment with PCP impaired social interactions in rats, as has been previously reported. These results suggest that NMDA antagonists have modulatory effects on the central vasopressinergic system and social interaction. Less