Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating that is impaired in many clinical conditions, including schizophrenia. The inbred Roman high-avoidance (RHA) rats, compared to their low-avoidance (RLA) counterparts, show distinct schizophrenia-like phenotypes, such as spontaneous deficits in PPI accompanied by decreased medial prefrontal cortex (mPFC) activity and volume. Schizophrenia-like deficits are usually attenuated by antipsychotic drugs, but these drugs often produce severe side effects. In order to reduce these side effects, the neuropeptide oxytocin has been proposed as an alternative natural antipsychotic for schizophrenia. Here, we examined the effects of peripheral oxytocin administration (saline, 0.04, and 0.2 mg/kg) on PPI in the RHA vs. RLA rats, as well as in the outbred heterogeneous stock (HS) rats. Our results showed that oxytocin increased PPI in the HS rats and attenuated PPI deficits in the RHA rats, but it did not significantly affect PPI in the RLAs. To explore whether these divergent effects were associated with differences in oxytocinergic mechanisms, we analyzed gene expression of the oxytocin receptor (OXTR) and the regulator of oxytocin release (CD38) in the mPFC of the Roman rats. Consistent with the differential oxytocin effects on PPI (RHA > RLA), constitutive CD38 expression was reduced in the RHA rats compared to the RLAs, while oxytocin administration increased OXTR expression in both strains. Overall, the present work reveals that oxytocin administration shows antipsychotic-like effects on PPI in outbred and inbred rats, and it suggests that these effects may be related to basal differences in oxytocin-mediated mechanisms in the mPFC.

惊吓反应的前脉冲抑制 (PPI) 是感觉运动门控的量度，在包括精神分裂症在内的许多临床病症中受损。与低回避 (RLA) 大鼠相比，近交罗马高回避 (RHA) 大鼠表现出明显的精神分裂症样表型，例如 PPI 自发性缺陷伴随内侧前额叶皮层 (mPFC) 活动和体积减少。精神分裂症样缺陷通常由抗精神病药物减轻，但这些药物通常会产生严重的副作用。为了减少这些副作用，已经提出神经肽催产素作为精神分裂症的替代天然抗精神病药。在这里，我们检查了外周催产素给药（盐水、0.04 和 0.2 mg/kg）对 RHA 与 RLA 大鼠 PPI 的影响，以及在远交异种股票（HS）大鼠中。我们的研究结果表明，催产素增加了 HS 大鼠的 PPI 并减轻了 RHA 大鼠的 PPI 缺陷，但它对 RLA 中的 PPI 没有显着影响。为了探索这些不同的影响是否与催产素机制的差异有关，我们分析了催产素受体的基因表达。OXTR ) 和罗马大鼠 mPFC 中的催产素释放调节剂 ( CD38 )。与催产素对 PPI (RHA > RLA) 的不同影响一致，与 RLA相比，RHA 大鼠的组成性CD38表达降低，而催产素给药增加了两种菌株中的OXTR表达。总体而言，目前的工作表明，催产素给药对远交和近交大鼠的 PPI 表现出抗精神病样作用，这表明这些作用可能与 mPFC 中催产素介导机制的基础差异有关。