Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA.
Psychopharmacology (Berl). 2018 Dec;235(12):3535-3543. doi: 10.1007/s00213-018-5078-2. Epub 2018 Oct 21.
Previous work has shown that some mouse strains (e.g., DBA/2J [D2]) readily develop robust ethanol-induced conditioned place preference (CPP) while others (e.g., C57BL/6J [B6]) do not. Though commonly interpreted as a difference between strains in sensitivity to ethanol reward, other explanations for this finding are possible.
To explore the hypothesis that variation in sensitivity to contextual cues underlies CPP differences, the present work investigated ethanol-induced CPP in D2 and B6 mice trained with a standard tactile (floor) cue procedure compared to mice trained with tactile plus visual-spatial cues.
In an unbiased CPP procedure, mice were assigned to either a single element cue (one-compartment apparatus with tactile cue presented in the dark) or multi-modal cues (two-compartment apparatus with distinct tactile floors and lights on). To track CPP development, mice received preference tests during training in addition to a final test.
Adding visual-spatial cues accelerated CPP acquisition in both D2 and B6 mice. However, this enhancement was observed after just one ethanol-conditioning trial in D2 mice, but was observed only after four ethanol-conditioning trials in B6 mice. Differences between groups trained with single or multi-modal cues disappeared as conditioning reached asymptote, with D2 mice showing a more rapid loss of the effect and a higher maximum CPP.
Although multi-modal cues produce more rapid conditioning, their inability to reduce or eliminate strain differences in CPP supports the interpretation that these strains differ in their sensitivity to ethanol reward.
先前的研究表明，一些小鼠品系（例如 DBA/2J [D2]）很容易产生强烈的乙醇诱导的条件位置偏好（CPP），而其他品系（例如 C57BL/6J [B6]）则不会。尽管这通常被解释为对乙醇奖赏的敏感性存在品系差异，但对于这一发现还有其他可能的解释。
为了探究以下假说，即对环境线索的敏感性差异是 CPP 差异的基础，本研究在 D2 和 B6 小鼠中进行了乙醇诱导的 CPP 研究，这些小鼠通过标准触觉（地板）线索程序进行训练，而其他小鼠则通过触觉加视觉空间线索进行训练。
在无偏 CPP 程序中，将小鼠分配到单一元素线索（一个隔间装置，在黑暗中呈现触觉线索）或多模态线索（两个隔间装置，具有独特的触觉地板和灯光）。为了追踪 CPP 的发展，除了最后的测试外，在训练期间，小鼠还接受了偏好测试。
在 D2 和 B6 小鼠中，添加视觉空间线索加速了 CPP 的获得。然而，这种增强只在 D2 小鼠的一个乙醇条件作用试验后观察到，而在 B6 小鼠中仅在四个乙醇条件作用试验后观察到。在达到适应的渐近线时，接受单一或多模态线索训练的组之间的差异消失，D2 小鼠表现出更快的效应丧失和更高的最大 CPP。
尽管多模态线索可以更快地产生条件作用，但它们无法减少或消除 CPP 中品系差异，这支持了这些品系对乙醇奖赏的敏感性存在差异的解释。
