Aging reduces the sensitivity to the reinforcing efficacy of morphine

Abstract

The US geriatric population is growing and using more opioids than ever before. The purpose of this study was to determine whether aging influenced the reinforcing efficacy of morphine in male and female rats using a rodent intravenous self-administration paradigm. Male and female aged (20-24 months) and young (2-4 months) Wistar rats were tested at 2 doses of morphine (0.75 mg/kg/infusion and 0.25 mg/kg/infusion). During 10 days of self-administration, aged rats took significantly less morphine than their younger counterparts at the 0.25 mg/kg/infusion dose. Aged males also earned significantly fewer infusions on a progressive ration reinforcement schedule at this dose, suggesting that the reinforcing efficacy of morphine is decreased for this group at this dose. These effects dissipated when a separate group of animals had access to the 0.75 mg/kg/infusion dose for both sexes. Our results indicate that morphine is less reinforcing at lower doses in aged male, but not female rats. This research has potential clinical implications for the chronic treatments involving opioids in aged individuals.

Keywords: Aging; Drug sensitivity; Intravenous self-administration; Opioid use disorder; Reinforcing efficacy.

Figure 1.. Aging decreases morphine taking at a low dose of morphine.

A. Full experimental timeline of morphine self-administration (IVSA). Following 2 days of habituation, animals had access to morphine on a fixed ratio (FR) 1 reinforcement schedule at either 0.25mg/kg/infusion or 0.75mg/kg/infusion (two separate cohorts). The animals then had access to morphine on a progressive ratio schedule for 1 day at the same dose (either 0.25mg/kg/infusion or 0.75mg/kg/infusion). B. Aged males took less morphine during the FR1 phase at the 0.25mg/kg/infusion dose. C. Aged males had lowed progressive ratio breakpoints. D. Aged females self-administered less morphine than control females on and FR1 schedule. E. On a progressive ratio schedule, aging did not impact the motivation to earn morphine infusion for females at the 0.25mg/kg/infusion dose. F. At the higher dose of morphine (0.75mg/kg/infusion) dose, aged and control males earned similar number of infusions on the FR1 reinforcement schedule and on the PR schedule (G). H. Aged females earned fewer infusions of morphine at the 0.75mg/kg/infusion dose on the FR1. I. On a PR schedule, young and aged females showed similar breakpoints at the 0.75mg/kg/infusion dose.