Department of Psychology, University of Colorado Denver, Denver, USA.
Psychopharmacology (Berl). 2012 Feb;219(4):1089-97. doi: 10.1007/s00213-011-2438-6. Epub 2011 Aug 24.
We have previously described a model in which adult outbred male Sprague-Dawley rats are classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on acute cocaine-induced open-field activation. This model revealed important individual differences in cocaine's effects, including that LCRs exhibited greater responding than HCRs on a progressive ratio schedule of cocaine reinforcement. However, no LCR/HCR differences in acquisition of cocaine self-administration (0.25 mg/kg/12 s infusion) were observed under these conditions.
To determine if LCRs and HCRs differ in the effectiveness of cocaine to function as a reinforcer under a broader range of conditions, the present study assessed the acquisition of cocaine self-administration (fixed ratio 1 schedule of reinforcement) as a function of i.v. cocaine dose (0.1875, 0.375, 0.5, 1, or 1.5 mg/kg/6 s infusion).
LCRs and HCRs did not differ significantly on any measure of acquisition examined, including the day to meet acquisition criterion, percent acquired, and cocaine intake. The effect of dose on percent acquired and rate of acquisition peaked at the 1-mg/kg/infusion dose of cocaine. In contrast, the effect of dose on cocaine intake was linear, with the highest rate of intake occurring at the 1.5-mg/kg/infusion dose of cocaine.
LCRs and HCRs do not appear to differ in their acquisition of cocaine-reinforced operant responding across a range of cocaine doses, including conditions that lead to high levels of cocaine intake.
我们之前描述了一个模型,该模型基于急性可卡因诱导的开放场激活,将成年杂交雄性 Sprague-Dawley 大鼠分为低或高可卡因反应者(分别为 LCR 或 HCR)。该模型揭示了可卡因作用的重要个体差异,包括 LCR 在可卡因强化的渐进比率方案中比 HCR 表现出更大的反应。然而,在这些条件下,未观察到 LCR/HCR 在可卡因自我给药(0.25mg/kg/12s 输注)获得中的差异。
为了确定 LCR 和 HCR 在更广泛的条件下,可卡因作为强化物的有效性是否存在差异,本研究评估了可卡因自我给药(强化比 1 方案)的获得情况,作为静脉内可卡因剂量(0.1875、0.375、0.5、1 或 1.5mg/kg/6s 输注)的函数。
LCR 和 HCR 在任何被检查的获得测量上都没有显著差异,包括达到获得标准的天数、获得的百分比和可卡因摄入量。剂量对获得百分比和获得率的影响在 1mg/kg/输注剂量的可卡因时达到峰值。相比之下,剂量对可卡因摄入量的影响是线性的,在 1.5mg/kg/输注剂量的可卡因时摄入量最高。
LCR 和 HCR 在可卡因强化操作性反应的获得方面似乎没有差异,包括导致可卡因摄入量高的条件。