Memory and motivation: an exploration of the synaptic and systems interactions underlying the formation and extinction of addictive memories

在加拿大，药物滥用给社会和家庭生活带来了沉重的负担，部分原因是其对过早死亡和残疾的破坏性影响。此外，由于其对卫生保健和刑事司法系统的影响，对经济造成了重大压力。根据加拿大药物滥用中心的一项调查，加拿大药物滥用的总社会成本估计为398亿美元，反映出加拿大每年每个活着的人的成本超过1 000美元。药物滥用是一个必须在各个方面加以解决的问题。与使用酒精、烟草和非法药物有关的问题的潜在解决办法必须像问题本身和受其影响的人一样微妙和多样化。药物滥用是一种复杂的疾病，涉及环境因素、多个大脑区域和大量神经化学因素的相互作用，这些因素被认为会增加个体对成瘾行为的易感性。本作品试图揭示这些微妙和复杂之处。随着获得最先进的设备来全面操作12个操作室（即“斯金纳箱”），本提案中提出的实验旨在确定在成瘾行为的发展，维持和终止过程中经历实质性变化的大脑机制，其中一些可能是药物滥用问题的基础。在这项研究的过程中，将利用大鼠进行临床前研究，以更充分地了解成瘾背后的大脑神经化学和结构变化。这些实验将研究大脑功能的各个层面，从神经化学物质和分子，到脑细胞，再到整个大脑和行为有机体。这些研究将为更清楚地了解药物滥用和成瘾过程背后的多种神经成分提供基础，并导致治疗方法的发展，以减少这些毁灭性的疾病。

In Canada, substance abuse imparts a measurable burden on society and family life in part as a result of its devastating effects on premature death and disability. In addition, there is a significant strain on the economy due to its impact on the health care and criminal justice systems. According to a Canadian Centre on Substance Abuse survey, the overall social cost of substance abuse in Canada is estimated to be $39.8 billion, reflecting a cost of over $1,000 to every living person in Canada each year. Substance abuse is a problem that must be addressed on all fronts. Potential solutions to problems associated with the use of alcohol, tobacco and illegal drugs must be as subtle and diverse as the problems themselves and the people they affect. Substance abuse is a complex disorder which involves the interaction of environmental factors, multiple brain regions and a vast array of neurochemical factors that are believed to increase the susceptibility of an individual to addictive behavior. The present work attempts to shed some light on these subtleties and complexities. With the acquisition of state-of-the art equipment to fully operate 12 operant chambers (i.e., 'Skinner' boxes), the experiments laid out in this proposal are set to determine the brain mechanisms that undergo substantial changes during the development, maintenance and termination of addictive-like behaviors, some of which may underlie substance abuse problems. During the course of this research, preclinical studies using rats will be utilized to more fully understand the neurochemical and structural changes in the brain that underlie addiction. The experiments will study all levels of brain function from neurochemicals and molecules, through brain cells, to the whole brain and the behaving organism. These studies will provide a foundation for a clearer understanding of the multiple neural components underlying the substance abuse and addiction process and lead to the development of treatments to curtail these devastating disorders.