Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake

The goal of this study was to address a critical gap in the literature regarding age-dependent effects in opioid (remifentanil and fentanyl) self-administration. Male and female C57Bl/6J and C57Bl/6NJ mice were divided into young (mean: 19 weeks) and old (mean: 101 weeks) groups and were trained to self-administer intravenous fentanyl or remifentanil in daily operant sessions. Acquisition, intake, and cue-responding after forced abstinence were measured for both drugs, and a dose-response curve and dose-escalation were conducted for remifentanil and fentanyl, respectively. Surprisingly, old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. Baseline intake of remifentanil was also greater in old mice compared to the young group; however, we did not see increased intake of fentanyl with age at either dose tested. Furthermore, old mice showed greater responding for cues previously associated with remifentanil after a forced abstinence, but this result is not observed with fentanyl.

本研究旨在填补阿片类药物（opioid）自身给药行为的年龄依赖性效应相关文献中的关键研究空白。实验选取雄性及雌性C57Bl/6J与C57Bl/6NJ品系小鼠，分为青年组（平均周龄19周）与老年组（平均周龄101周），通过每日操作性训练环节，使其掌握静脉注射芬太尼（fentanyl）或瑞芬太尼（remifentanil）的自身给药行为。针对两种药物，本研究分别测定了其自身给药的习得情况、给药摄入量以及强迫戒断后的线索诱发反应；同时分别针对瑞芬太尼与芬太尼开展剂量反应曲线实验与剂量递增实验。令人意外的是，相较于青年小鼠，老年小鼠能够更快且更精准地掌握两种药物的自身给药行为。老年小鼠的瑞芬太尼基线摄入量同样高于青年组；但在两个测试剂量下，均未观察到芬太尼摄入量随年龄增长而升高的现象。此外，强迫戒断后，老年小鼠对先前与瑞芬太尼关联的环境线索的反应强度显著更高，但该结果在芬太尼实验中并未出现。