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

Abstract

Opioid abuse and overdose are major societal issues, and use of opioids among the elderly is increasing at a rapid rate. Despite this increase in opioid use, overdose, and use disorders among the elderly, little is known about abuse potential in a healthy aged population due to technical difficulties with 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 (19 weeks) and old (101 weeks) 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. Old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. While baseline intake was greater in the old compared to young mice self-administering remifentanil, we did not see an increased intake with age at either dose of fentanyl 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 this was not seen for 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.