Department of Psychology, The University of Texas at Arlington, Arlington, TX 76019, USA.
Pharmacol Biochem Behav. 2012 Nov;103(1):76-82. doi: 10.1016/j.pbb.2012.08.005.
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.
临床研究表明，焦虑症会增加物质使用障碍的风险。然而，很少有研究直接评估焦虑作为处理奖励刺激的易感性因素。Wistar-Kyoto (WKY) 大鼠被提出作为焦虑易感性的模型，因为它在新异和社会环境中表现出极端的行为抑制；然而，它表现出矛盾的快速主动回避学习，对消退有抵抗力。本研究旨在描述 WKY 大鼠可卡因条件性位置偏爱 (CPP) 的获得和维持。在一系列三个实验中的第一个实验中，成年雄性 WKY 和 Sprague Dawley (SD) 大鼠在交替的日子里接受了六次可卡因（3、5、10、15mg/kg）或盐水的配对。SD 大鼠对测试的四种可卡因剂量均产生了可卡因诱导的 CPP。相比之下，WKY 大鼠在条件化 3、5 和 10mg/kg 时表现出 CPP，但对 15mg/kg 剂量没有偏好。接下来，单独的大鼠组接受了扩展的 CPP 范式，包括获得、消退和复燃阶段。大鼠在交替的日子里接受可卡因和盐水的条件化，使用 6/6（如上所述）或 4/4 条件化方案。SD 和 WKY 大鼠都用 6/6 条件化方案获得了持久的 CPP。4/4 条件化方案的结果表明，SD 大鼠而不是 WKY 大鼠获得了 CPP。SD 大鼠在可卡因引发的复燃测试中的偏好分数与测试前分数显著不同，表明该组 CPP 的复燃。矛盾的是，WKY 大鼠在药物引发的复燃测试中表现出对可卡因条件性奖励作用的潜在敏感化。总之，WKY 大鼠似乎对高剂量的可卡因更敏感，并且比 SD 大鼠需要更多的药物经验来获得偏好。
