Cocaine self-administration under fixed and progressive ratio schedules of reinforcement: comparison of C57BL/6J, 129X1/SvJ, and 129S6/SvEvTac inbred mice.
Cocaine self-administration under fixed and progressive ratio schedules of reinforcement: comparison of C57BL/6J, 129X1/SvJ, and 129S6/SvEvTac inbred mice.
复制标题
固定和渐进比例强化方案下的可卡因自我给药：C57BL/6J、129X1/SvJ 和 129S6/SvEvTac 近交小鼠的比较。
DOI：
10.1007/s00213-005-0207-0
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发表时间：
2006
影响因子：
3.4
通讯作者：
Caine,SBarak
中科院分区：
文献类型：
--
作者：
Thomsen,Morgane;Caine,SBarak
基本原理组合菌株来产生突变小鼠可能会掩盖有关目标基因的结论。具体而言，与分别常用于 ES 细胞和育种的 C57BL/6 菌株相比，可卡因在 129 个亚菌株中的增强作用可能降低。 目的我们测试了可卡因的增强作用在 C57BL/6J 菌株与 129、129X1/SvJ 和 129S6/SvEvTac 两个亚菌株之间不同的假设。方法为了评估和减少性能差异，建立了操作反应液体食物作为强化剂，并根据固定和渐进的比例计划进行评估。然后根据两种方案确定静脉注射可卡因自我给药的剂量效应函数。最后，将强化和非强化的操纵器颠倒过来，以使用先前的非强化反应来评估自我给药的获得。结果相对于 C57BL/6J 小鼠，129X1/SvJ 小鼠表现出低量食物和可卡因强化剂的强化效果降低。尽管 129S6/SvEvTac 小鼠的操作行为获得延迟且食物浓度效应函数右移，但 C57BL/6J 和 129S6/SvEvTac 小鼠的可卡因自我给药剂量效应函数相当。在逆转过程中，高剂量的可卡因显然在所有三种品系中都起到了积极的强化作用。 结论相对于 C57BL/6J 小鼠，可卡因的强化作用在 129X1/SvJ 小鼠中减弱，但仅适用于低可卡因剂量，并且在食物强化中观察到类似的情况。 129S6/SvEvTac 小鼠比 C57BL/6J 小鼠需要更广泛的操作训练，但获得后，可卡因的增强作用在两个品系中相似。我们认为，在基因靶向研究中观察到的可比表型可能是由遗传背景造成的，而更深刻或本质上不同的表型可能更可靠地归因于靶向突变。
RationaleCombining strains to generate mutant mice may obscure conclusions regarding the targeted gene. Specifically, cocaine may have reduced reinforcing effects in 129 substrains compared to the C57BL/6 strain, commonly used for ES cells and breeding, respectively.ObjectivesWe tested the hypothesis that reinforcing effects of cocaine differ between the C57BL/6J strain and two substrains of 129, 129X1/SvJ and 129S6/SvEvTac.MethodsTo assess and reduce performance differences, operant responding was established with liquid food as a reinforcer and evaluated under fixed and progressive ratio schedules. Dose–effect functions for intravenous cocaine self-administration were then determined under both schedules. Finally, reinforced and nonreinforced manipulanda were reversed to assess acquisition of self-administration using a previously nonreinforced response.ResultsRelative to C57BL/6J mice, 129X1/SvJ mice showed decreased reinforcing effects of low-magnitude food and cocaine reinforcers. Dose–effect functions for cocaine self-administration were comparable between C57BL/6J and 129S6/SvEvTac mice, despite delayed acquisition of operant behaviors and rightward shifts in the food concentration–effect functions in 129S6/SvEvTac mice. A high cocaine dose clearly served as a positive reinforcer in all three strains in a reversal procedure.ConclusionsRelative to C57BL/6J mice, the reinforcing effects of cocaine were diminished in 129X1/SvJ mice, but only for low cocaine doses, and a similar profile was observed with food reinforcement. 129S6/SvEvTac mice required more extensive operant training than C57BL/6J mice did, but after acquisition, reinforcing effects of cocaine were similar in the two strains. We suggest that comparable phenotypes observed in gene-targeting studies may result from genetic background, whereas more profound or qualitatively different phenotypes may be more confidently attributed to targeted mutations.