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

Although opioid abuse is more prevalent in young individuals, opioid use, overdose, and use disorders continue to climb at a rapid rate among the elderly. Little is known about abuse potential in a healthy aged population, in part due to technical and logistical difficulties testing intravenous self-administration in aged rodents. The goal of this study was to address the critical gap in the literature regarding age-dependent differences in opioid (remifentanil and fentanyl) self-administration between old and young mice. Male and female mice were grouped into young (mean: 19 weeks) and old (mean: 101 weeks), and were trained to self-administer intravenous fentanyl or remifentanil in daily sessions. In both old and young mice, acquisition, intake, and cue-responding after forced abstinence were measured for both drugs, and a dose-response curve (remifentanil) and dose-escalation (fentanyl) were conducted. Surprisingly, old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. Baseline intake of remifentanil was also substantially greater in old mice compared to their young counterparts; however, we did not see increased intake of fentanyl with age at either dose tested. Further, compared to young mice, the old mice showed a greater incubation of responding for cues previously associated with remifentanil after a forced abstinence, but again this was not observed with fentanyl. Together these data suggest that an aged population may have an increased drug-abuse vulnerability for opioids compared to young counterparts and underscore the importance of future work on mechanisms responsible for this increased vulnerability.