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Assessing learned associations between conditioned cocaine reward and environmental stimuli in the Wistar Kyoto rat

机译：评估Wistar Kyoto大鼠中可卡因奖励与环境刺激之间的学习关联

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摘要

Clinical studies demonstrate that anxiety disorders increase the risk of substance use disorder. However, few studies have directly assessed anxiety as a vulnerability factor in processing of rewarding stimuli. The Wistar-Kyoto (WKY) rat has been proposed as a model of anxiety vulnerability because it exhibits extreme behavioral inhibition in novel and social environments; yet, it displays paradoxical rapid active avoidance learning that is resistant to extinction. The present study was designed to characterize the acquisition and persistence of cocaine conditioned place preference (CPP) in WKY rats. In the first of a series of three experiments, adult male WKY and Sprague Dawley (SD) rats were given six pairings of cocaine (3, 5, 10, 15 mg/kg) or saline on alternating days. SD rats developed cocaine-induced CPP to each of the four doses of cocaine tested. In contrast, WKY rats demonstrated CPP when conditioned with 3, 5, and 10 mg/kg, but displayed no preference to the 15 mg/kg dose. Next, separate groups of rats were subject to an extended CPP paradigm, which included acquisition, extinction and reinstatement phases. Rats were conditioned with cocaine and saline on alternating days using either a 6/6 (as above) or 4/4 conditioning regimen. Both SD and WKY rats acquired a lasting CPP with the 6/6 conditioning regimen. Results from the 4/4 conditioning regimen show that SD, but not WKY, rats acquired CPP. Preference scores for SD rats during the cocaine primed reinstatement test were significantly different from pretest scores indicating reinstatement of CPP in this group. Paradoxically, WKY rats demonstrated a latent sensitization to the conditioned rewarding effects of cocaine during the drug-primed reinstatement test. Taken together, WKY rats appear to be more sensitive to high doses of cocaine and need more experience with the drug to acquire a preference than SD rats.
机译：临床研究表明，焦虑症会增加药物滥用症的风险。但是，很少有研究直接将焦虑作为奖励性刺激过程中的易损因素。 Wistar-Kyoto（WKY）大鼠已被提出作为焦虑脆弱性的模型，因为它在新型和社交环境中表现出极端的行为抑制能力。然而，它却显示出抗拒灭绝的自相矛盾的快速主动回避学习。本研究旨在描述可卡因条件性位置偏爱（CPP）在WKY大鼠中的获取和持久性。在这三个实验的第一个实验中，成年雄性WKY和Sprague Dawley（SD）大鼠隔天交替服用六对可卡因（3、5、10、15 mg / kg）或生理盐水。 SD大鼠在四剂可卡因中均产生了可卡因诱导的CPP。相反，WKY大鼠在分别以3、5和10 mg / kg的剂量条件下表现出CPP，但对15 mg / kg的剂量没有偏爱。接下来，对单独的大鼠组进行扩展的CPP范式，包括获取，灭绝和恢复阶段。使用6/6（如上）或4/4调理方案，每隔一天用可卡因和盐水调理大鼠。 SD和WKY大鼠均采用6/6调理方案获得了持久的CPP。 4/4调理方案的结果表明，SD（而非WKY）大鼠获得了CPP。在可卡因引发的恢复试验中，SD大鼠的优先评分与表明可恢复CPP的前测评分显着不同。矛盾的是，在药物引发的恢复试验期间，WKY大鼠对可卡因的条件性奖励作用表现出潜在的致敏作用。两者合计，WKY大鼠似乎比SD大鼠对高剂量可卡因更敏感，并且需要更多的药物经验来获得偏爱。

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