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Chronic opioid exposure differentially modulates oxycodone self‐administration in male and female rats
- Source :
- Addiction biology
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Withdrawal from opioid painkillers can produce short-lived physical symptoms and protracted psychological symptoms including anxiety and depressive-like states that often lead to opioid misuse and opioid use disorder (OUD). Studies testing the hypothesis that opioid withdrawal potentiates the reinforcing effects of opioid self-administration (SA) are largely inconclusive and have focused on males. Although some clinical evidence indicates that women are more likely than men to misuse opioids to self-medicate, preclinical studies in both sexes are lacking. Based on clinical reports, we hypothesized that withdrawal from escalating-dose morphine injections that approximates a prescription painkiller regimen would lead to increased oxycodone SA to a greater extent in female compared to male rats. After escalating-dose morphine (5–30 mg/kg or vehicle, twice/day for 12 days), rats underwent a 2-week abstinence period during which withdrawal signs were measured. The impact of this treatment was assessed on oxycodone SA acquisition, maintenance, dose response, and progressive ratio responding, with additional analyses to compare sexes. We found that both sexes expressed somatic withdrawal, whereas only males demonstrated hyperalgesia in the warm water tail flick assay. During SA acquisition, males with prior morphine exposure took significantly more oxycodone than females. Finally, females with prior morphine exposure demonstrated the lowest motivation to SA oxycodone in the progressive ratio test. Contrary to our initial hypothesis, our findings suggest that prior opioid exposure increases vulnerability to initiate misuse more in males and decreases the reinforcing efficacy of oxycodone in females.
- Subjects :
- Male
Narcotics
sex differences
media_common.quotation_subject
Medicine (miscellaneous)
Physiology
Self Administration
Article
somatic withdrawal
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Animals
Medicine
hyperalgesia
media_common
Pharmacology
Morphine
business.industry
opioid use disorder
Opioid use disorder
Abstinence
Opioid-Related Disorders
medicine.disease
Rats
Substance Withdrawal Syndrome
030227 psychiatry
Psychiatry and Mental health
progressive ratio
Opioid
Hyperalgesia
Anxiety
Female
medicine.symptom
intravenous self-administration
business
Self-administration
Reinforcement, Psychology
Oxycodone
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 13691600 and 13556215
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Addiction Biology
- Accession number :
- edsair.doi.dedup.....015d4fbb1066ab9761f01618ecefdc29
- Full Text :
- https://doi.org/10.1111/adb.12973