Effect of yohimbine on reinstatement of operant responding in rats is dependent on cue contingency but not food reward history
Effect of yohimbine on reinstatement of operant responding in rats is dependent on cue contingency but not food reward history
复制标题
DOI：
10.1111/adb.12164
复制
发表时间：
2015-07-01
影响因子：
3.4
通讯作者：
Calu, Donna J.
中科院分区：
文献类型：
--
作者：
Chen, Yu-Wei;Fiscella, Kimberly A.;Calu, Donna J.
育亨宾是一种α -2肾上腺素受体拮抗剂，在许多研究中被用作啮齿动物、猴子和人类的药理学应激源。近年来，育亨宾已成为药物和食物寻求恢复研究中最常见的应激操作。然而，育亨宾促进奖励寻求的条件范围很广，明显大于间歇性足震等压力源。在这里，我们解决了关于育亨宾对奖励寻求恢复的影响的两个基本问题：(1)药物对操作性反应的影响是否取决于先前的奖励历史或提示偶然性；(2)在恢复研究中通常使用的条件下，育亨宾是厌恶的还是奖励的。我们还使用体内微透析来确定育亨宾对伏隔核（NAc）和内侧前额叶皮层（mPFC）多巴胺水平的影响。我们发现育himine诱导的（0.5、1.0、2.0mg/kg）操作反应的大小在恢复测试中严重依赖于杠杆按压和离散声光提示传递之间的偶然性，而不是先前训练期间的食物奖励历史。我们还发现育亨宾（2mg/kg）不会引起条件性场所厌恶。最后，我们发现育亨宾适度地增加了mPFC中的多巴胺水平，而不是NAc。结果表明育亨宾对恢复研究中操作性反应的影响可能独立于偶然的自我给予食物或药物奖励的历史，可能与通常认为的育亨宾的应激样作用无关。
Yohimbine is an alpha-2 adrenoceptor antagonist that has been used in numerous studies as a pharmacological stressor in rodents, monkeys and humans. Recently, yohimbine has become the most common stress manipulation in studies on reinstatement of drug and food seeking. However, the wide range of conditions under which yohimbine promotes reward seeking is significantly greater than that of stressors like intermittent footshock. Here, we addressed two fundamental questions regarding yohimbine's effect on reinstatement of reward seeking: (1) whether the drug's effect on operant responding is dependent on previous reward history or cue contingency, and (2) whether yohimbine is aversive or rewarding under conditions typically used in reinstatement studies. We also used in vivo microdialysis to determine yohimbine's effect on dopamine levels in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). We found that the magnitude of yohimbine-induced (0.5, 1.0, 2.0mg/kg) operant responding during the reinstatement tests was critically dependent on the contingency between lever pressing and discrete tone-light cue delivery but not the previous history with food reward during training. We also found that yohimbine (2mg/kg) did not cause conditioned place aversion. Finally, we found that yohimbine modestly increased dopamine levels in mPFC but not NAc. Results suggest that yohimbine's effects on operant responding in reinstatement studies are likely independent of the history of contingent self-administration of food or drug rewards and may not be related to the commonly assumed stress-like effects of yohimbine.