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Sex Differences in the Ability to Predict and Treat Opiate Abuse


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Due to improved battlefield medicine, the majority of Soldiers who are wounded survive and treated with prescription opioid painkillers. This award has two goals: to test a novel means (Distress Intolerance) of predicting risk for prescription opioid abuse, and to test a pharmacological compound (CRF receptor antagonist) for prevention of prescription opioid abuse and addiction. We use male and female rats that were exposed to an experimenter-administered regimen of escalating-dose morphine (or saline) injections. This design allows us to be sensitive to sex differences, which exist in human drug abusers, and it allows us to determine if a model of physician-prescribed opioids alters vulnerability to subsequent abuse. In this second year of funding we have completed the first goal and have begun testing the changes to the self-administration paradigm we obtained IACUC and ACURO approval for. Specifically, for Aim 2, we are now going to test the effects of the CRF receptor antatonist antalarmin on escalation of oxycodone intake in a long-access self-administration paradigm. To date, we found that certain measures of Distress Intolerance (e.g., warm water tail flick latency and acoustic startle response) in drug-nave rats were significantly correlated with the amount of oxycodone rats self-administered during the acquisition phase. After completion of Aim 1,we found that prior morphine experience in males, but not females, increased oxycodone self-administration. In conclusion, our findings suggest 1) Distress Intolerance measures can be taken before deployment and used to help decide whether a Soldier would be at risk for developing an opioid use disorder, and 2) prior exposure to, and withdrawal from, a regimen of opioids (administered in a manner akin to a prescription in people) increases vulnerability of males, but not females, to increased addiction-like behavior.



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