George F R
Behavioral and Biochemical Genetics, Preclinical Pharmacology Branch, NIDA Addiction Research Center, Baltimore, MD.
J Addict Dis. 1991;10(1-2):127-39. doi: 10.1300/J069v10n01_09.
Vulnerability to substance abuse is an important emerging issue. A critical aspect of this phenomenon is the degree to which individuals who abuse one substance are likely to abuse other substances, alone or in combination with each other. The extent to which several distinct drugs will come to serve as positive reinforcers within genetically defined subjects defines their commonality. Questions in this area are directed at determining whether reinforcement from and abuse of alcohol and other drugs define variations within a single behavioral phenomenon, or whether reinforcement and abuse must be individually defined for each substance involved. Findings related to this commonality issue are now emerging from the areas of pharmacogenetics and operant drug self-administration. Previous studies have shown that ethanol can be readily established as a positive reinforcer in LEWIS rats, as well as C57BL/6J mice. In low ethanol preferring F344 rats, ethanol maintains significant but low levels of responding. Ethanol does not maintain lever pressing behavior in BALB/cJ mice, and is avoided in DBA/2J mice. Initial findings reported in this paper show that these genotypic patterns of reinforcement from ethanol appear to correlate highly with patterns of reinforcement from cocaine and opiates. From these findings it is concluded that (1) there exist important genetic determinants of drug reinforced behavior; and (2) drug seeking behaviors maintained by ethanol, cocaine and opiates may have at least some common biological determinants.
药物滥用易感性是一个重要的新出现问题。这一现象的一个关键方面是滥用一种药物的个体滥用其他药物(单独或相互组合)的可能性程度。几种不同药物在基因定义的个体中作为阳性强化物的程度定义了它们的共性。该领域的问题旨在确定酒精和其他药物的强化作用及滥用是定义单一行为现象中的变异,还是每种相关药物的强化作用和滥用必须单独定义。与这一共性问题相关的研究结果现正从药物遗传学和操作性药物自我给药领域中浮现。先前的研究表明,乙醇在LEWIS大鼠以及C57BL/6J小鼠中很容易被确立为阳性强化物。在低乙醇偏好的F344大鼠中,乙醇维持着显著但较低水平的反应。乙醇在BALB/cJ小鼠中不能维持压杆行为,并且在DBA/2J小鼠中被回避。本文报道的初步研究结果表明,乙醇强化作用的这些基因型模式似乎与可卡因和阿片类药物的强化作用模式高度相关。从这些研究结果可以得出结论:(1)存在药物强化行为的重要遗传决定因素;(2)由乙醇、可卡因和阿片类药物维持的觅药行为可能至少有一些共同的生物学决定因素。