Carroll Marilyn E, Morgan Andrew D, Anker Justin J, Perry Jennifer L, Dess Nancy K
Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA.
Behav Pharmacol. 2008 Sep;19(5-6):435-60. doi: 10.1097/FBP.0b013e32830c3632.
A positive relationship between the consumption of sweetened dietary substances (e.g. saccharin and sucrose) and drug abuse has been reported in both the human and other animal literature. The proposed genetic contribution to this relationship has been based on evidence from behavioral, neurobiological, and linkage studies in heterogeneous and homogeneous animal populations. Initial work in several laboratories indicated that rodents that are selected for high alcohol consumption also display an increased preference for sweets compared with low alcohol-consuming animals. More recently, Sprague-Dawley rats have been selectively bred based on high saccharin (HiS) or low saccharin (LoS) consumption, and these lines represent an ideal opportunity to determine whether a reciprocal genetic relationship exists between the consumption of sweetened substances and self-administration of drugs of abuse. The purpose of this review is to examine a series of studies on the HiS and LoS rats for drug-seeking and drug-taking behavior using laboratory animal models that represent critical phases of drug abuse in humans. The data support the hypothesis that sweet consumption and drug self-administration are closely related and genetically influenced. Other characteristics of HiS and LoS rats are discussed as possible mediators of the genetic differences such as activity, impulsivity, novelty reactivity, stress, and emotionality. The interaction of sweet preference with biological variables related to drug abuse, such as age, sex, and hormonal influences, was considered, as they may be additive vulnerability factors with consumption of sweet substances. In the studies that are discussed, the HiS and LoS lines emerge as ideal addiction-prone and addiction-resistant models, respectively, with vulnerability or resilience factors that will inform prevention and treatment strategies for drug abuse.
在人类和其他动物文献中均报道了甜味饮食物质（如糖精和蔗糖）的摄入与药物滥用之间存在正相关关系。关于这种关系的遗传贡献的提议是基于对异质和同质动物群体进行的行为、神经生物学及连锁研究的证据。几个实验室的初步研究表明，与低酒精摄入量的动物相比，被选择用于高酒精摄入量的啮齿动物对甜味的偏好也有所增加。最近，基于高糖精（HiS）或低糖精（LoS）摄入量对斯普拉格-道利大鼠进行了选择性培育，这些品系为确定甜味物质的摄入与滥用药物的自我给药之间是否存在相互遗传关系提供了理想的机会。本综述的目的是利用代表人类药物滥用关键阶段的实验动物模型，对一系列关于HiS和LoS大鼠的觅药和用药行为的研究进行考察。数据支持了甜味摄入与药物自我给药密切相关且受遗传影响这一假设。还讨论了HiS和LoS大鼠的其他特征，如活动、冲动性、对新事物的反应性、应激和情绪等，这些可能是遗传差异的潜在调节因素。还考虑了甜味偏好与与药物滥用相关的生物学变量（如年龄、性别和激素影响）之间的相互作用，因为它们可能是甜味物质摄入的附加易感性因素。在讨论的研究中，HiS和LoS品系分别成为理想的易成瘾和抗成瘾模型，其易感性或恢复力因素将为药物滥用的预防和治疗策略提供参考。
