Minneapolis Medical Research Foundation, Minneapolis, MN, United States; Department of Psychology, University of Minnesota, Minneapolis, MN, United States.
Minneapolis Medical Research Foundation, Minneapolis, MN, United States.
Pharmacol Biochem Behav. 2018 Mar;166:48-56. doi: 10.1016/j.pbb.2018.01.008. Epub 2018 Feb 2.
Understanding factors contributing to individual differences in opioid addiction vulnerability is essential for developing more effective preventions and treatments. Sensation seeking has been implicated in addiction to several drugs of abuse, yet its relationship with individual differences in opioid addiction vulnerability has not been well established. The primary goal of this study was to evaluate the relationship between locomotor activity in a novel environment, a preclinical model of sensation-seeking, and individual differences in acquisition of i.v. morphine self-administration (SA) in rats. A secondary goal was to evaluate the relationship between activity and elasticity of demand (reinforcing efficacy) for morphine measured using a behavioral economic approach. Following an initial locomotor activity screen, animals were allowed to acquire morphine SA at a unit dose of 0.5 mg/kg/infusion in 4 hour/day sessions (Experiment 1) or 0.2 mg/kg/infusion in 2 hour/day sessions (Experiment 2) until infusion rates were stable. Unit price was subsequently manipulated via progressive reductions in unit dose (Experiment 1) or increases in response requirement per infusion (Experiment 2). Activity levels were not correlated with acquisition of morphine SA in either experiment. Morphine consumption was generally well described by an exponential demand function in both experiments (R values > 0.95 for rats as a group), but activity did not correlate with behavioral economic measures. Locomotor activity in a novel environment did not predict individual differences in acquisition of morphine SA. These data complement findings from some human studies and suggest that the role of sensation seeking in individual differences in opioid addiction vulnerability may be limited.
了解导致个体对阿片类药物成瘾易感性差异的因素对于开发更有效的预防和治疗方法至关重要。感觉寻求与几种滥用药物的成瘾有关，但它与个体对阿片类药物成瘾易感性的差异之间的关系尚未得到很好的确定。本研究的主要目的是评估在新环境中的运动活动，即感觉寻求的临床前模型，与大鼠静脉注射吗啡自我给药（SA）获得的个体差异之间的关系。次要目标是评估使用行为经济学方法测量的活动与吗啡需求的弹性（强化效力）之间的关系。在初始运动活动筛选后，动物被允许在 4 小时/天的时间段内以 0.5mg/kg/输注的单位剂量（实验 1）或 2 小时/天的时间段内以 0.2mg/kg/输注的单位剂量（实验 2）获得吗啡 SA，直到输注率稳定。随后通过逐步降低单位剂量（实验 1）或增加每个输注的反应要求（实验 2）来操纵单价。在两个实验中，活动水平均与吗啡 SA 的获得无关。在两个实验中，吗啡的消耗通常都可以很好地用指数需求函数来描述（作为一个群体的大鼠的 R 值> 0.95），但活动与行为经济学测量无关。在新环境中的运动活动并不能预测吗啡 SA 获得的个体差异。这些数据补充了一些人类研究的发现，并表明感觉寻求在个体对阿片类药物成瘾易感性差异中的作用可能有限。
