Richard Jocelyn M, Armstrong Anne, Newell Bailey, Muruganandan Preethi, Janak Patricia H, Saunders Benjamin T
Department of Neuroscience, University of Minnesota, Minneapolis, MN.
Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, MN.
bioRxiv. 2024 Mar 14:2024.03.14.585064. doi: 10.1101/2024.03.14.585064.
Cues paired with alcohol can be potent drivers of craving, alcohol-seeking, consumption, and relapse. While the ventral pallidum is implicated in appetitive and consummatory responses across several reward classes and types of behaviors, its role in behavioral responses to Pavlovian alcohol cues has not previously been established. Here, we tested the impact of optogenetic inhibition of ventral pallidum on Pavlovian-conditioned alcohol-seeking in male Long Evans rats. Rats underwent Pavlovian conditioning with an auditory cue predicting alcohol delivery to a reward port and a control cue predicting no alcohol delivery, until they consistently entered the reward port more during the alcohol cue than the control cue. We then tested the within-session effects of optogenetic inhibition during 50% of cue presentations. We found that optogenetic inhibition of ventral pallidum during the alcohol cue reduced port entry likelihood and time spent in the port, and increased port entry latency. Overall, these results suggest that normal ventral pallidum activity is necessary for Pavlovian alcohol-seeking.
与酒精相关的线索可能是引发渴望、寻求酒精、饮酒及复发的强大驱动力。虽然腹侧苍白球在多种奖励类别和行为类型的食欲和满足反应中发挥作用，但其在对巴甫洛夫式酒精线索的行为反应中的作用此前尚未明确。在此，我们测试了腹侧苍白球的光遗传学抑制对雄性长 Evans 大鼠巴甫洛夫条件性酒精寻求行为的影响。大鼠接受巴甫洛夫条件反射训练，一个听觉线索预示着酒精会被输送到奖励端口，另一个对照线索预示着不会有酒精输送，直到它们在酒精线索出现时比对照线索出现时更频繁地进入奖励端口。然后，我们在 50% 的线索呈现过程中测试了光遗传学抑制的 session 内效应。我们发现，在酒精线索出现期间对腹侧苍白球进行光遗传学抑制会降低进入端口的可能性和在端口停留的时间，并增加进入端口的潜伏期。总体而言，这些结果表明，正常的腹侧苍白球活动对于巴甫洛夫式酒精寻求行为是必要的。
