Intrinsic and synaptic mechanisms mediating the neuronal effects of toluene

介导甲苯神经元效应的内在和突触机制

• 批准号: 371835-2009
• 负责人: McKay, Bruce
• 金额: $ 2.55万
• 依托单位: Wilfrid Laurier University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=504184
• 关键词: Intrinsic; synaptic; mechanisms; mediating; neuronal

Solvents like toluene are widely abused by Canadian children and adolescents to achieve a euphoric state; toluene is also a toxic compound present in specific Canadian workplaces associated with the lumber, printing or painting industries. The behavioural changes and ultimately the long-term addiction that follows self-administration of these chemicals are likely related to acute and chronic modifications of brain function. The exact mechanisms by which toluene modifies brain function are incompletely understood, although one hypothesis is that these chemicals acutely and chronically modify the electrical (ion channels and action potentials) and chemical (neurotransmitters and synapses) signals that specific types of brain cells in specific regions of the brain use to transmit and store information. The research program of Dr. McKay is dedicated to addressing this hypothesis. Dr. McKay is interested in identifying the ion channels and neurotransmitter receptors that mediate the effects of the abused solvent toluene in neurons of the brain essential for specific types of learning. Given that toluene is often abused by very young children, Dr. McKay is further interested in assessing the potential differential vulnerability of young brains compared to mature brains to the long-term effects of toluene. The research program will provide highly qualified personnel the opportunity to use state-of-the-art electrophysiology and imaging tools to integrate across multiple levels of discourse from single ion channels to neurons to networks of neurons and ultimately to behaviour, thereby providing them with the specificity and breadth of knowledge and skills to prepare them for careers in academia, industry and government in Canada and elsewhere. The research will pursue novel hypothesis-driven studies and answer questions that will interest many scientists who study how abused drugs / chemicals change brain function, and may one day be helpful for the numerous Canadians who very early in their lives begin to abuse chemicals like toluene or are exposed to toluene in their workplaces.

像甲苯这样的溶剂被加拿大的儿童和青少年广泛滥用，以达到一种愉悦的状态；甲苯也是一种有毒化合物，存在于加拿大与木材、印刷或油漆行业有关的特定工作场所。自我服用这些化学物质后的行为改变和最终的长期成瘾可能与大脑功能的急性和慢性改变有关。甲苯改变大脑功能的确切机制尚不完全清楚，尽管有一种假设是，这些化学物质会急性和慢性地改变大脑特定区域特定类型的脑细胞用来传递和存储信息的电信号（离子通道和动作电位）和化学信号（神经递质和突触）。麦凯博士的研究项目致力于解决这一假设。麦凯博士感兴趣的是识别离子通道和神经递质受体，这些离子通道和神经递质受体介导了对特定学习类型至关重要的大脑神经元中滥用溶剂甲苯的影响。鉴于甲苯经常被非常年幼的儿童滥用，麦凯博士进一步感兴趣的是评估与成熟大脑相比，年轻大脑对甲苯长期影响的潜在脆弱性。该研究项目将为高素质的人员提供使用最先进的电生理学和成像工具的机会，以整合从单个离子通道到神经元到神经元网络，最终到行为的多个层面的话语，从而为他们提供特异性和广度的知识和技能，为他们在加拿大和其他地方的学术界、工业界和政府的职业生涯做好准备。这项研究将进行新颖的假设驱动的研究，并回答许多研究滥用药物/化学物质如何改变大脑功能的科学家感兴趣的问题，并且可能有一天对许多在生命早期就开始滥用甲苯等化学物质或在工作场所接触甲苯的加拿大人有所帮助。