Ambrosio E., Goldberg S.R., Elmer G.I.
Departamento de Psicobiologia, Universidad Nacional de Educación a Distancia (UNED), Ciudad Universitaria, Madrid, Spain, E-28040.
Behav Pharmacol. 1995 Apr;6(3):229-237.
There is a significant degree of individual variability in response to drugs of abuse. A goal of behavior genetic studies has been to determine the extent to which observed heterogeneity in drug use can be attributed to genetic and environmental factors and to identify the neurobiological factors involved in vulnerability. Recent hypotheses regarding the predictive value of spontaneous locomotor activity in the acquisition of drug-reinforced behavior are amenable to testing using a behavior genetics approach. Genetic differences in locomotor response to a novel environment were determined in naive and catheterized Lewis, F344, NBR and ACI rats. Operant drug-reinforced behavior was examined in a 23h access paradigm in which each lever press by a rat produced a 1mg/kg injection of morphine with a 30s timeout period (FR 1:TO 30"). Acquisition (7 days), extinction (6 days) and reacquisition (7 days) of morphine self-administration behavior was investigated in all four inbred strains. Large genetic differences in the rate of acquisition and extinction of morphine self-administration were found. Lewis rats responded at high rates beginning in the first two days, whereas F344 rats initially responded at low rates and responding increased gradually over seven days. NBR and ACI rats responded at intermediate levels. When vehicle was substituted for drug there was a significant effect of genotype on the rate of extinction; F344 and ACI increased responding to greater than 175% of drug-response levels, whereas the Lewis response rate decreased gradually and NBR response rate decreased immediately during the first several days. When drug was available again, rates of reacquisition did not differ from original acquisition rates. Drug maintained significantly greater amounts of behavior than vehicle in the Lewis, F344 and NBR rats and was thus shown to serve as a positive reinforcer in these three strains under these conditions. There was a significant genetic correlation among strains between drug intake during the first five days of acquisition and spontaneous locomotor response to a novel environment in catheterized rats. Only the ACI rats showed a significant within-strain correlation. The positive relationship between rate of acquisition of self-administration behavior and locomotor activity suggests that these two traits are influenced by common or closely linked genes. To this end, the neurobiological substrates that mediate spontaneous locomotor behavior under these environmental conditions may act, in part, as a template for determining the neurobiological substrates that mediate the relative rate of acquisition of morphine-taking behavior under these conditions.
个体对滥用药物的反应存在显著差异。行为遗传学研究的一个目标是确定观察到的药物使用异质性在多大程度上可归因于遗传和环境因素，并确定涉及易感性的神经生物学因素。最近关于自发运动活动在药物强化行为习得中的预测价值的假说适合用行为遗传学方法进行检验。在未经验证和插管的Lewis、F344、NBR和ACI大鼠中确定了对新环境的运动反应的遗传差异。在23小时获取范式中检查操作性药物强化行为，其中大鼠每次按压杠杆都会注射1mg/kg吗啡，并伴有30秒的超时时间（FR 1:TO 30"）。在所有四个近交系中研究了吗啡自我给药行为的习得（7天）、消退（6天）和重新习得（7天）。发现吗啡自我给药的习得和消退速率存在很大的遗传差异。Lewis大鼠从最初两天开始反应率就很高，而F344大鼠最初反应率很低，且在七天内反应逐渐增加。NBR和ACI大鼠反应处于中等水平。当用赋形剂替代药物时，基因型对消退速率有显著影响；F344和ACI大鼠的反应增加到药物反应水平的175%以上，而Lewis大鼠的反应率逐渐下降，NBR大鼠的反应率在最初几天立即下降。当再次提供药物时，重新习得的速率与原始习得速率没有差异。在Lewis、F344和NBR大鼠中，药物维持的行为量显著大于赋形剂，因此表明在这些条件下，药物在这三个品系中起到了正强化物的作用。在插管大鼠中，品系之间在习得的前五天药物摄入量与对新环境的自发运动反应之间存在显著的遗传相关性。只有ACI大鼠表现出显著的品系内相关性。自我给药行为习得速率与运动活动之间的正相关表明，这两个性状受共同或紧密连锁基因的影响。为此，在这些环境条件下介导自发运动行为的神经生物学底物可能部分地作为模板，用于确定在这些条件下介导吗啡摄取行为相对习得速率的神经生物学底物。
