Stimulus Complexity and Mouse Strain Drive Escalation of Operant Sensation Seeking Within and Across Sessions in C57BL/6J and DBA/2J Mice
Stimulus Complexity and Mouse Strain Drive Escalation of Operant Sensation Seeking Within and Across Sessions in C57BL/6J and DBA/2J Mice
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DOI：
10.3389/fnbeh.2019.00286
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发表时间：
2020-01-10
影响因子：
3
通讯作者：
Mittleman, Guy
中科院分区：
文献类型：
--
作者：
Dickson, Price E.;Mittleman, Guy
感觉寻求是一种与物质使用相关的可遗传特征；这些特征背后的共同遗传机制在很大程度上是未知的。感觉寻求和物质使用的关系具有实际意义，因为发现驱动感觉寻求的基因可以揭示驱动物质使用的基因，并且在小鼠中量化感觉寻求比量化自愿药物使用具有更高的吞吐量和更少的技术挑战。为了充分了解驱动感觉寻求的遗传机制，首先要了解驱动感觉寻求的非遗传因素。在本研究中，我们使用操纵性感觉寻求范式来评估刺激复杂性对C57BL/6J和DBA/2J小鼠感觉寻求的影响。这些菌株是BXD重组近交系小鼠小组的创始人，该小组使发现驱动表型变异的基因成为可能。这项研究得出了四个主要结论。首先，研究中使用的所有感觉刺激，无论复杂性或刺激方式的数量，都作为C57BL/6J和DBA/2J小鼠的增强剂。第二，对于C57BL/6J和DBA/2J小鼠，寻求高复杂性感觉刺激的感觉显著大于寻求低复杂性感觉刺激的感觉。第三，对于C57BL/6J和DBA/2J小鼠，当使用中等或高复杂性的多模式感觉刺激时，感觉寻求在会话中显著升级，但当使用低复杂性的单模式感觉刺激时，感觉寻求没有显著升级。最后，DBA/2J品系小鼠的感觉寻求强度和感觉寻求在会话内升级的幅度都显著高于C57BL/6J品系小鼠。总而言之，这些发现表明，刺激的复杂性和遗传背景推动了操作员感觉寻求在会话内和跨会话的升级，BXD重组近交系小鼠小组可以用来发现这些现象背后的遗传机制。
Sensation seeking is a heritable trait that is genetically correlated with substance use; the shared genetic mechanisms underlying these traits are largely unknown. The relationship of sensation seeking and substance use has practical importance because discovering genes that drive sensation seeking can reveal genes driving substance use, and quantification of sensation seeking in mice is higher throughput and less technically challenging than quantification of volitional drug use. In order to fully understand the genetic mechanisms driving sensation seeking, it is critical to first understand the nongenetic factors driving sensation seeking. In the present study, we used the operant sensation seeking paradigm to assess the effects of stimulus complexity on sensation seeking in C57BL/6J and DBA/2J mice. These strains are the founders of the BXD recombinant inbred mouse panel which enables the discovery of genes driving phenotypic variation. This study led to four principal conclusions. First, all sensory stimuli used in the study, regardless of complexity or number of stimulus modalities, served as reinforcers for C57BL/6J and DBA/2J mice. Second, for both C57BL/6J and DBA/2J mice, sensation seeking for a high complexity sensory stimulus was significantly greater than sensation seeking for a low complexity sensory stimulus. Third, for both C57BL/6J and DBA/2J mice, sensation seeking escalated significantly within-session when a multimodal sensory stimulus of medium or high complexity was used but not when a unimodal sensory stimulus of low complexity was used. Finally, both the magnitude of sensation seeking and the magnitude of within-session escalation of sensation seeking were significantly greater in mice from the DBA/2J strain relative to mice from the C57BL/6J strain. Collectively, these findings indicate that stimulus complexity and genetic background drive escalation of operant sensation seeking within and across sessions, and that the BXD recombinant inbred mouse panel can be used to discover the genetic mechanisms underlying these phenomena.