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

Amanda L Sharpe ¹, Laci R Liter ², Darius Donohue ³

⁰Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences.

Biorxiv : the Preprint Server for Biology +

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September 16, 2024

View abstract on PubMed

Summary

Older mice exhibit increased vulnerability to opioid drug abuse, learning to self-administer remifentanil and fentanyl faster than younger mice. This suggests a higher risk of opioid use disorders in the elderly population.

Area Of Science

Neuroscience
Gerontology
Pharmacology

Background

Opioid use, overdose, and use disorders are increasing rapidly among the elderly.
Limited understanding exists regarding the abuse potential of opioids in healthy aged populations.
Technical challenges hinder the study of intravenous drug self-administration in aged rodents.

Purpose Of The Study

To investigate age-dependent differences in opioid (remifentanil and fentanyl) self-administration between old and young mice.
To address the critical gap in literature concerning opioid abuse potential in aged populations.
To compare acquisition, intake, and cue-responding for opioids in young versus old mice.

Main Methods

Male and female mice were grouped into young (19 weeks) and old (101 weeks).
Mice were trained for intravenous self-administration of fentanyl or remifentanil in daily sessions.
Acquisition, intake, cue-responding after abstinence, dose-response, and dose-escalation curves were measured.

Main Results

Old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice.
Baseline remifentanil intake was significantly higher in old mice compared to young mice.
Old mice showed greater incubation of responding for remifentanil-associated cues after abstinence, unlike with fentanyl.

Conclusions

Aged populations may possess increased vulnerability to opioid drug abuse compared to younger individuals.
These findings highlight the importance of studying the mechanisms underlying age-related increases in opioid vulnerability.
Further research is crucial to understand and mitigate opioid risks in the elderly.