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

Abstract

Although opioid abuse is more prevalent in young individuals, the rates of opioid use, overdose, and use disorders continue to climb among the elderly. Little is known about the biology underlying 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 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 was not observed with fentanyl. This first report of opioid self-administration in greater than 20-month-old mice suggests that old mice have an increased vulnerability for opioid use compared to younger counterparts, underscoring the importance of future work to uncover the biological mechanisms that are responsible.