Schizophrenia and Nicotine Addiction: Analysis of genetic mouse models

精神分裂症和尼古丁成瘾：基因小鼠模型分析

• 批准号: 146395062
• 负责人: Professor Dr. Andreas Zimmer
• 金额: --
• 依托单位: Institut für Molekulare Psychiatrie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/146395062?language=en
• 关键词: Schizophrenia; Nicotine; Addiction; Analysis; genetic

This project addresses the molecular mechanisms that contribute to the high comorbidity of schizophrenia and nicotine addiction, by investigating the effect of nicotine in animal models with a deletion or transgenic over-expression of schizophrenia risk genes (DISC1, G72/G30, NRG3). We hypothesize that schizophrenic patients consume nicotine as a form of self-medication. Thus, acute and chronic nicotine administration might have beneficial effects on the behavioural deficits in paradigms for schizophrenia-like symptoms that have been observed in the genetic mouse models. Our alternative, not mutually exclusive, hypothesis is that the rewarding and/or addictive properties of nicotine are enhanced in genetic models of schizophrenia. This hypothesis will be tested by assessing the rewarding properties of nicotine in a place preference and operant self-administration paradigm. Further we will assess somatic signs of nicotine withdrawal after chronic administration. We will start to evaluate the molecular mechanisms that contribute to the anticipated differential effects of nicotine in these mouse models, by assessing nicotine receptor levels and downstream signalling pathways. These molecular studies will be guided by our (still unpublished) discovery of nicotine-induced transcriptional changes in specific brain regions, in the context of a NIH-funded project.

该项目通过研究尼古丁在精神分裂症风险基因（DISC 1，G72/G30，NRG 3）缺失或转基因过度表达的动物模型中的作用，探讨导致精神分裂症和尼古丁成瘾高度共病的分子机制。我们假设精神分裂症患者服用尼古丁是一种自我药物治疗。因此，急性和慢性尼古丁给药可能对遗传小鼠模型中观察到的精神分裂症样症状范例中的行为缺陷具有有益影响。我们的另一种假设是，尼古丁的奖励和/或成瘾特性在精神分裂症的遗传模型中得到增强。将通过评估尼古丁在位置偏好和操作性自我给药范式中的奖励特性来检验这一假设。此外，我们将评估长期给药后尼古丁戒断的躯体体征。我们将通过评估尼古丁受体水平和下游信号传导通路，开始评估导致这些小鼠模型中尼古丁预期差异效应的分子机制。这些分子研究将以我们在NIH资助的项目中发现的尼古丁诱导的特定大脑区域转录变化（尚未发表）为指导。

项目成果

Lipidomics reveals dysfunctional glycosynapses in schizophrenia and the G72/G30 transgenic mouse

• DOI: 10.1016/j.schres.2014.08.029
• 发表时间: 2014-11-01
• 期刊: SCHIZOPHRENIA RESEARCH
• 影响因子: 4.5
• 作者: Wood, Paul L.;Filiou, Michaela D.;Turck, Christoph W.
• 通讯作者: Turck, Christoph W.

Dynorphins regulate the strength of social memory

• DOI: 10.1016/j.neuropharm.2013.10.023
• 发表时间: 2014-02-01
• 期刊: NEUROPHARMACOLOGY
• 影响因子: 4.7
• 作者: Bilkei-Gorzo, A.;Mauer, D.;Zimmer, A.
• 通讯作者: Zimmer, A.

N-acetyl Cysteine Treatment Rescues Cognitive Deficits Induced by Mitochondrial Dysfunction in G72/G30 Transgenic Mice

• DOI: 10.1038/npp.2011.109
• 发表时间: 2011-06
• 期刊: Neuropsychopharmacology
• 影响因子: 7.6
• 作者: D. Otte;B. Sommersberg;A. Kudin;Catalina Guerrero;Önder Albayram;M. Filiou;Pamela Frisch;Öznur Yilmaz;E. Drews;C. Turck;A. Bilkei-Gorzo;W. Kunz;H. Beck;A. Zimmer