GENETIC-DIFFERENCES IN THE REWARDING AND ACTIVATING EFFECTS OF MORPHINE AND ETHANOL
GENETIC-DIFFERENCES IN THE REWARDING AND ACTIVATING EFFECTS OF MORPHINE AND ETHANOL
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DOI：
10.1007/bf02245166
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发表时间：
1992-06-01
影响因子：
3.4
通讯作者：
PRATHER, LK
中科院分区：
文献类型：
--
作者：
CUNNINGHAM, CL;NIEHUS, DR;PRATHER, LK
在位置条件化实验中，研究了基因型对吗啡和乙醇的奖赏效应和自发激活效应的影响。两个近交系小鼠品系（C57 BL/6J和DBA/2J）暴露于差异条件反射程序，其中每只小鼠接受四对独特的地板刺激，并IP注射吗啡（0，2.5，5或10 mg/kg）或乙醇（0，1，2，3或4 g/kg）。不同的地板刺激与盐水配对。条件反射试验持续30分钟，每个实验结束时，在没有药物的情况下进行地板偏好测试。在雅阁与以前的研究，吗啡诱发的剂量依赖性增加活动在条件反射，是更大的C57 BL/6J小鼠比DBA/2J小鼠。相比之下，乙醇产生的活性的剂量依赖性增加，是更大的DBA/2J比C57 BL/6J小鼠。两种品系对吗啡均表现出条件性位置偏爱，但只有DBA/2J品系对乙醇表现出条件性位置偏爱。未见条件性位置厌恶。使用这两种药物，DBA/2J小鼠获得了更强的位置偏好条件反射，支持对药物奖励的敏感性受基因型影响的一般结论。同一基因型对两种不同药物的奖励效应更敏感，这一事实支持了药物奖励生物机制的共同性假设。虽然乙醇研究的结果支持成瘾的精神兴奋剂理论关于药物诱导的激活和奖励之间关系的预测，但吗啡研究的结果并不支持。条件性位置偏好中的应变差异的方向与先前在药物消费和偏好研究中报道的应变差异的基础上可能预测的方向相反，这表明药物消费的遗传差异可能无法准确反映药物的吸收后动机效应。
The influence of genotype on the rewarding and locomotor activating effects of morphine and ethanol was examined in the place conditioning paradigm. Two inbred mouse strains (C57BL/6J and DBA/2J) were exposed to a differential conditioning procedure in which each mouse received four pairings of a distinctive floor stimulus with IP injection of morphine (0, 2.5, 5 or 10 mg/kg) or ethanol (0, 1, 2, 3 or 4 g/kg). A different floor stimulus was paired with saline. Conditioning trials lasted 30 min and each experiment concluded with a floor preference test in the absence of drug. In accord with previous studies, morphine evoked a dose-dependent increase in activity during conditioning that was greater in C57BL/6J mice than in DBA/2J mice. In contrast, ethanol produced a dose-dependent increase in activity that was greater in DBA/2J than in C57BL/6J mice. Both strains showed conditioned place preference with morphine, but only the DBA/2J strain showed conditioned place preference with ethanol. No conditioned place aversion was seen. With both drugs, stronger place preference conditioning was obtained in DBA/2J mice, supporting the general conclusion that sensitivity to drug reward is influenced by genotype. The fact that the same genotype is more sensitive to the rewarding effects of two different drugs supports theories postulating commonality in the biological mechanisms of drug reward. Although the outcome of the ethanol study supports predictions of the psychomotor stimulant theory of addiction concerning the relationship between drug-induced activation and reward, the outcome of the morphine study does not. The direction of the strain difference in conditioned place preference is opposite to what might be predicted on the basis of strain differences previously reported in drug consumption and preference studies, suggesting that genetic differences in drug consumption may not accurately reflect postabsorptive motivational effects of drug.