McDonald Allison J, Alonso-Lozares Isis, Rauh Vasco, van Mourik Yvar, Schetters Dustin, De Vries Taco J, Marchant Nathan J
Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Front Behav Neurosci. 2021 Oct 21;15:739681. doi: 10.3389/fnbeh.2021.739681. eCollection 2021.
In humans, stimuli associated with alcohol availability can provoke relapse during abstinence. In this study, we investigated the role of discriminative stimuli (DS) in the control of alcohol seeking in two types of behavioral tests. The first test examined the ability of an alcohol-associated DS to promote alcohol seeking (relapse) after punishment-imposed abstinence in the presence of a different DS. Following this, we tested whether the differentially associated DS can promote and suppress alcohol self-administration in a within-session discrimination task. During the within-session discrimination task, we also tested the rate of alcohol self-administration when two DS are presented in a compound. We first trained Long-Evans male rats ( = 24) to self-administer alcohol in the presence of one DS (reward-associated discriminative stimulus, rewDS) and then punished that behavior in the presence of a different DS (punishment-associated discriminative stimulus, punDS). On the test, we found that rats tested with the rewDS showed higher alcohol seeking than rats tested with the punDS. This result shows that a single Cue DS can promote alcohol seeking in a manner comparable to contexts. Subsequently, we trained 16 of these rats in a within-session trial-based discrimination task, comprised of intervening 2-min trials of rewDS, punDS, or conflict with rewDS and punDS in compound and a reduced probability of punishment. We found that alcohol self-administration is bi-directionally regulated by the rewDS and punDS. In conflict trials, alcohol self-administration was at a rate that was intermediate between the rewDS and punDS trials. In a final test, rats were presented with one of the three trial conditions and perfused for Fos immunohistochemistry. We found Fos expression was higher in the rats tested in the conflict condition in three interconnected sub-cortical brain regions. This study demonstrated the important role that alcohol-associated DS plays an important role in promoting relapse to alcohol seeking after punishment-imposed abstinence. We also implemented a within-session discrimination task that allows for the study of alcohol seeking under motivational conflict, which may be relevant for alcohol use despite negative consequences. The results from the Fos data suggest that higher alcohol seeking in approach-avoidance motivational conflict is associated with activation of sub-cortical regions but not cortical regions.
在人类中，与酒精可得性相关的刺激可在戒酒期间引发复饮。在本研究中，我们在两种行为测试中研究了辨别性刺激（DS）在控制酒精觅求行为中的作用。第一个测试考察了与酒精相关的DS在不同DS存在的情况下，促进惩罚性戒酒期后酒精觅求（复饮）的能力。在此之后，我们测试了差异关联的DS在会话内辨别任务中是否能促进和抑制酒精自我给药。在会话内辨别任务期间，我们还测试了两种DS复合呈现时酒精自我给药的速率。我们首先训练24只Long-Evans雄性大鼠在一种DS（奖励相关辨别性刺激，rewDS）存在的情况下自我给药酒精，然后在不同DS（惩罚相关辨别性刺激，punDS）存在的情况下对该行为进行惩罚。在测试中，我们发现用rewDS测试的大鼠比用punDS测试的大鼠表现出更高的酒精觅求行为。这一结果表明，单一的线索DS能够以与情境类似的方式促进酒精觅求。随后，我们对其中16只大鼠进行了基于会话内试验的辨别任务训练，该任务包括2分钟的rewDS、punDS试验，或rewDS与punDS复合的冲突试验以及惩罚概率降低的试验。我们发现酒精自我给药受到rewDS和punDS的双向调节。在冲突试验中，酒精自我给药的速率介于rewDS和punDS试验之间。在最后一项测试中，给大鼠呈现三种试验条件之一，并进行灌注以进行Fos免疫组织化学检测。我们发现在三个相互连接的皮质下脑区中，处于冲突条件下测试的大鼠Fos表达更高。本研究证明了与酒精相关的DS在惩罚性戒酒期后促进酒精觅求复饮中所起的重要作用。我们还实施了一项会话内辨别任务，该任务允许在动机冲突下研究酒精觅求，这可能与尽管有负面后果仍饮酒的行为相关。Fos数据的结果表明，在趋避动机冲突中更高的酒精觅求与皮质下区域而非皮质区域的激活有关。
