Robertson Stephen H, Jutkiewicz Emily M
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.
Behav Pharmacol. 2020 Apr;31(2&3):207-215. doi: 10.1097/FBP.0000000000000550.
Previous research demonstrated that a remifentanil-associated stimulus facilitated the acquisition of a previously unlearned response; however, it is unclear how long a remifentanil-associated stimulus maintains conditioned reinforcing properties under conditions of daily testing. To address this gap, we exposed adult male rats to response-independent stimulus presentations and deliveries of remifentanil (1.0, 3.2, or 10.0 μg/kg/infusion). Rats either received the stimulus presentations and remifentanil deliveries together (Paired Pavlovian conditioning) or according to separate clocks (Random control group). In the sessions following Pavlovian conditioning, we allowed rats to emit nose-poke responses for the presentation of the stimulus alone and measured the extent to which the stimulus facilitated and maintained a previously unlearned response. We tested responding for the stimulus presentations across 28 daily sessions to assess the Pavlovian extinction (degradation of the drug-stimulus association) of the conditioned reinforcing properties of the remifentanil-associated stimulus. We observed the highest and most persistent levels of responding in rats with a Paired Pavlovian conditioning history at 3.2 and 10.0 μg/kg/infusion. In addition, we included analyses of the variability in responding for each group, which revealed individual differences in the susceptibility of the remifentanil-associated stimulus acting as a conditioned reinforcer. These findings demonstrate that a remifentanil-associated stimulus has the ability to sustain drug-seeking behavior and underscores the importance of Pavlovian conditioning in promoting drug abuse.
先前的研究表明，瑞芬太尼相关刺激促进了对先前未习得反应的习得；然而，尚不清楚在每日测试条件下，瑞芬太尼相关刺激保持条件强化特性的时间有多长。为了填补这一空白，我们让成年雄性大鼠接受与反应无关的刺激呈现以及瑞芬太尼（1.0、3.2或10.0μg/kg/输注）给药。大鼠要么同时接受刺激呈现和瑞芬太尼给药（配对巴甫洛夫条件反射），要么根据不同的时钟接受（随机对照组）。在巴甫洛夫条件反射后的实验环节中，我们让大鼠仅为了刺激呈现而发出鼻触反应，并测量刺激促进和维持先前未习得反应的程度。我们在28个每日实验环节中测试了对刺激呈现的反应，以评估瑞芬太尼相关刺激的条件强化特性的巴甫洛夫消退（药物 - 刺激关联的退化）。我们观察到，在配对巴甫洛夫条件反射历史的大鼠中，输注剂量为3.2和10.0μg/kg时，反应水平最高且最持久。此外，我们对每组反应的变异性进行了分析，这揭示了瑞芬太尼相关刺激作为条件强化物作用时易感性的个体差异。这些发现表明，瑞芬太尼相关刺激有能力维持觅药行为，并强调了巴甫洛夫条件反射在促进药物滥用中的重要性。
