Explicating Vulnerability and Resilience in Opioid Self-Administration in Middle Aged Rats

Mortality statistics in the United States show a steady increase in deaths due to prescription opioids over the past two decades, accompanied by a steep increase in heroin-related deaths from 2011 onward and deaths from synthetic opioids such as fentanyl from 2014 onward. An unexpectedly steep rise in the drug-related overdose rate for middle aged to older adults (50-65) in recent years has placed attention on the specific health risks for this population. Lethality data are but the tip of the iceberg of a much larger problem of opioid misuse and opioid use disorders. Therefore, these studies seek to explore how the middle age range of adulthood may influence opioid reward and addiction. The proposed studies will first determine any age-related differences in the involuntary effects of opioids on locomotion, nociception and thermoregulation. Studies will also use well established rat models of intravenous self- administration to model reward, initial acquisition and escalation of opioid drug seeking in young-adult and middle-aged rats. Additional experimentation will determine how brain reward may be modified across the lifespan and how these changes may produce liability for, or resilience against, prescription opioid abuse. Together, the Aims will investigate how the middle- aged adult developmental stage may influence in vivo sensitivity to oxycodone, heroin and fentanyl, relative to younger adulthood, and ultimately will investigate if middle age conveys any change in the propensity for self-administration of opioids.