Jacobs Edwin H, Smit August B, de Vries Taco J, Schoffelmeer Anton N M
Research Institute Neurosciences Vrije Universiteit, Drug Abuse Program, Department of Medical Pharmacology, VU Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Trends Pharmacol Sci. 2003 Nov;24(11):566-73. doi: 10.1016/j.tips.2003.09.006.
Increasing knowledge of the genome sequences of several organisms and the development of genome-wide, high-throughput screening techniques for gene expression are likely to generate a vast amount of data aimed at elucidating the molecular mechanisms of addiction. These findings are likely to have potential for future addiction pharmacotherapies. However, it is important to employ animal models that dissociate the molecular and cellular consequences of the direct pharmacological effects of addictive drugs from those that result from the cognitive processes associated with self-administration of these drugs. In this article, we suggest that the short-term and long-term neuroadaptive effects of addictive drugs in the brain depend crucially on the drug-exposure paradigm used [i.e. passive (non-contingent) drug exposure and active (contingent) self-administration]. This has important ramifications for future molecular and cellular studies of drug addiction.
对几种生物体基因组序列的了解不断增加,以及全基因组、高通量基因表达筛选技术的发展,可能会产生大量旨在阐明成瘾分子机制的数据。这些发现可能对未来的成瘾药物治疗具有潜在价值。然而,使用动物模型将成瘾药物直接药理作用的分子和细胞后果与这些药物自我给药相关认知过程所导致的后果区分开来很重要。在本文中,我们认为成瘾药物在大脑中的短期和长期神经适应性效应关键取决于所使用的药物暴露模式[即被动(非偶然)药物暴露和主动(偶然)自我给药]。这对未来成瘾药物的分子和细胞研究具有重要影响。