Thibault Christelle, Hassan Sajida, Miles Michael
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch cedex, France.
Addict Biol. 2005 Mar;10(1):53-62. doi: 10.1080/13556210412331308949.
The use of expression profiling with microarrays offers great potential for studying the mechanisms of action of drugs of abuse. Studies with the intact nervous system seem likely to be most relevant to understanding the mechanisms of drug abuse-related behaviours. However, the use of expression profiling with in vitro culture models offers significant advantages for identifying details of cellular signalling actions and toxicity for drugs of abuse. This study discusses general issues of the use of microarrays and cell culture models for studies on drugs of abuse. Specific results from existing studies are also discussed, providing clear examples of relevance for in vitro studies on ethanol, nicotine, opiates, cannabinoids and hallucinogens such as LSD. In addition to providing details on signalling mechanisms relevant to the neurobiology of drugs of abuse, microarray studies on a variety of cell culture systems have also provided important information on mechanisms of cellular/organ toxicity with drugs of abuse. Efforts to integrate genomic studies on drugs of abuse with both in vivo and in vitro models offer the potential for novel mechanistic rigor and physiological relevance.
利用微阵列进行表达谱分析为研究滥用药物的作用机制提供了巨大潜力。对完整神经系统进行的研究似乎最有助于理解与药物滥用相关行为的机制。然而，使用体外培养模型进行表达谱分析，对于确定滥用药物的细胞信号传导作用细节和毒性具有显著优势。本研究讨论了使用微阵列和细胞培养模型研究滥用药物的一般问题。还讨论了现有研究的具体结果，为乙醇、尼古丁、阿片类药物、大麻素和诸如麦角酸二乙酰胺（LSD）等致幻剂的体外研究提供了明确的相关实例。除了提供与滥用药物神经生物学相关的信号传导机制细节外，对各种细胞培养系统进行的微阵列研究还提供了有关滥用药物导致细胞/器官毒性机制的重要信息。将滥用药物的基因组研究与体内和体外模型相结合的努力，有望实现新的机制严谨性和生理相关性。
