Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Neuropeptides. 2010 Jun;44(3):233-9. doi: 10.1016/j.npep.2009.12.008. Epub 2010 Jan 25.
Recent research has highlighted a potential role for neuropeptide Y (NPY) and its Y(1) receptor in the development of schizophrenia. Genetic as well as molecular biological studies have demonstrated reduced levels of NPY in schizophrenia patients. Importantly, Y(1) receptors may mediate some of the potential effects of NPY on schizophrenia, as decreased Y(1) receptor expression has been found in the lymphocytes of schizophrenia patients. To clarify NPY's role in schizophrenia, we investigated a genetic animal model for Y(1) deficiency in regard to (i) acoustic startle response (ASR), (ii) habituation to ASR and (iii) sensorimotor gating [i.e. prepulse inhibition (PPI)] using two different PPI protocols. Mutant and wild type-like mice were screened for baseline behaviours and after pharmacological challenge with the psychotropic drugs dexamphetamine (DEX) and MK-801. Y(1) knockout mice (Y(1)(-/-)) showed a moderate reduction of the ASR and an impaired ASR habituation at baseline and after DEX treatment. The baseline PPI performance of Y(1) mutant mice was unaltered their response to DEX and MK-801 challenge was moderately different compared to control mice, which was dependent on the PPI protocol used. MK-801 challenge had a protocol-dependent differential effect in Y(1)(-/-) mice and DEX a more pronounced impact at the highest prepulse intensities. In conclusion, it appears that the Y(1) receptor influences the acoustic startle response and its habituation but does not play a major role in sensorimotor gating. Further explorations into the effects of Y(1) deficiency seem valid.
最近的研究强调了神经肽 Y (NPY)及其 Y(1)受体在精神分裂症发展中的潜在作用。遗传和分子生物学研究表明，精神分裂症患者的 NPY 水平降低。重要的是，Y(1)受体可能介导 NPY 对精神分裂症的一些潜在影响，因为精神分裂症患者的淋巴细胞中发现 Y(1)受体表达减少。为了阐明 NPY 在精神分裂症中的作用，我们研究了 Y(1)缺乏的遗传动物模型，研究了 (i) 听觉惊跳反应 (ASR)、(ii) ASR 习惯化和 (iii) 感觉运动门控[即 前脉冲抑制 (PPI)]，使用了两种不同的 PPI 方案。突变体和野生型样小鼠被筛选出基线行为，并在使用精神药物地昔帕明 (DEX) 和 MK-801 进行药物挑战后进行筛选。Y(1)敲除小鼠 (Y(1)(-/-)) 在基线和 DEX 治疗后表现出 ASR 中度降低和 ASR 习惯化受损。Y(1)突变小鼠的基线 PPI 表现没有改变，它们对 DEX 和 MK-801 挑战的反应与对照小鼠略有不同，这取决于所使用的 PPI 方案。MK-801 挑战在 Y(1)(-/-)小鼠中具有依赖方案的差异效应，DEX 在最高的前脉冲强度下具有更明显的影响。总之，似乎 Y(1)受体影响听觉惊跳反应及其习惯化，但在感觉运动门控中不起主要作用。进一步探索 Y(1)缺乏的影响似乎是合理的。
