Mohn Amy R, Yao Wei-Dong, Caron Marc G
Department of Cell Biology, HHMI Laboratories, Duke University Medical Centre, Box 3287, CARL Building, Durham, NC 27710, USA.
Neuropharmacology. 2004;47 Suppl 1:101-10. doi: 10.1016/j.neuropharm.2004.07.025.
Drug addiction is recognized as a mental disease affecting the brain's natural reward system. Drugs of abuse strongly activate reward structures in the brain and induce lasting changes in behavior that reflect changes in neuron physiology and biochemistry. With the ultimate goal of developing therapeutic interventions, it is of interest to determine the molecular and cellular components of motivation and reward, and identify those gene products that contribute to the process of drug addiction. Our laboratory has chosen three general genetic approaches to examine reward and addiction: reverse genetics to assess the role of candidate genes in drug responsiveness, forward genetics to discover novel regulators of dopamine transmission, and gene expression profiling to define gene sets in different brain structures that contribute to the molecular and neurobiological basis of reward.
药物成瘾被认为是一种影响大脑自然奖赏系统的精神疾病。滥用药物会强烈激活大脑中的奖赏结构,并诱发行为上的持久变化,这些变化反映了神经元生理和生物化学的改变。为了开发治疗干预措施这一最终目标,确定动机和奖赏的分子和细胞成分,并识别那些促成药物成瘾过程的基因产物是很有意义的。我们实验室选择了三种一般的遗传学方法来研究奖赏和成瘾:反向遗传学来评估候选基因在药物反应性中的作用,正向遗传学来发现多巴胺传递的新调节因子,以及基因表达谱分析来定义不同脑结构中有助于奖赏的分子和神经生物学基础的基因集。