Maddux Jean-Marie N, Chaudhri Nadia
Department of Psychology, Center for Studies in Behavioral Neurobiology/FRQS Groupe de recherche en neurobiologie comportementale, Concordia University, 7141 Sherbrooke Street West, Room SP 244, Montreal, QC, H4B-1R6, Canada.
Psychopharmacology (Berl). 2017 Feb;234(4):727-738. doi: 10.1007/s00213-016-4508-2. Epub 2016 Dec 23.
Nicotine enhances responding elicited by Pavlovian cues that predict positive outcomes.
We tested the hypothesis that nicotine acting at nicotinic acetylcholine receptors (nAChRs) would augment Pavlovian alcohol-seeking.
Male, Long-Evans rats with unrestricted access to food and water were acclimated to drinking 15% ethanol in their home cages and then given Pavlovian conditioning sessions in which each trial of a 15-s conditioned stimulus (CS, 12 trials/session) was paired with 0.2 ml of ethanol (unconditioned stimulus, US, 2.4 ml/session). Entries into a port where ethanol was delivered were used to assess conditioning. Control groups received explicitly unpaired trials of the CS and US. In experiment 1, systemic injections of saline (1 ml/kg) or nicotine (0.4 mg/kg, freebase) were administered before each session. In experiments 2 and 3, an identical regimen of saline or nicotine injections was administered before the start of Pavlovian conditioning sessions.
All paired groups acquired conditioned port-entry responding to the CS, indicative of Pavlovian alcohol-seeking, whereas unpaired control group did not. Pre-session nicotine injections increased CS port-entries relative to saline, only in the paired group. This nicotine-induced enhancement of Pavlovian alcohol-seeking was blocked by pre-treatment with the nAChR antagonist mecamylamine. Prior exposure to nicotine did not influence the subsequent acquisition of Pavlovian alcohol-seeking.
These findings highlight for the first time that nicotine acting at nAChRs augments Pavlovian alcohol-seeking, specifically in non-restricted rats. Individuals who smoke and drink may thus be particularly susceptible to alcohol cues that could trigger further drinking.
尼古丁会增强由预测积极结果的巴甫洛夫条件刺激所引发的反应。
我们检验了这样一个假设，即作用于烟碱型乙酰胆碱受体（nAChRs）的尼古丁会增强巴甫洛夫式的觅酒行为。
雄性长 Evans 大鼠可自由获取食物和水，先让它们适应在其笼舍中饮用 15%的乙醇，然后进行巴甫洛夫条件训练，每次 15 秒的条件刺激（CS，每秒 12 次试验）与 0.2 毫升乙醇（非条件刺激，US，每次训练 2.4 毫升）配对。进入提供乙醇的端口的次数用于评估条件反射。对照组接受 CS 和 US 明显不配对的试验。在实验 1 中，每次训练前进行生理盐水（1 毫升/千克）或尼古丁（0.4 毫克/千克，游离碱）的全身注射。在实验 2 和 3 中，在巴甫洛夫条件训练开始前进行相同的生理盐水或尼古丁注射方案。
所有配对组都获得了对 CS 的条件性端口进入反应，表明存在巴甫洛夫式的觅酒行为，而未配对的对照组则没有。仅在配对组中，训练前注射尼古丁相对于生理盐水增加了 CS 端口进入次数。这种尼古丁诱导的巴甫洛夫式觅酒行为增强被 nAChR 拮抗剂美加明预处理所阻断。先前接触尼古丁并不影响随后巴甫洛夫式觅酒行为的获得。
这些发现首次强调，作用于 nAChRs 的尼古丁会增强巴甫洛夫式的觅酒行为，特别是在非限制大鼠中。因此，吸烟且饮酒的个体可能特别容易受到可能引发进一步饮酒的酒精线索的影响。
