Sex and heredity are determinants of drug intake in a novel model of rat oral oxycodone self‐administration

The steady rise in prescription opioids such as oxycodone has led to a virulent epidemic of widespread abuse and deaths in the United States; approximately 80% of affected individuals initiate the habitual use of oxycodone by using prescription oral oxycodone. Given the importance of drug pharmacoki...

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Bibliographic Details
Published in:Genes, brain and behavior brain and behavior, 2021-11, Vol.20 (8), p.e12770-n/a
Main Authors: Sharp, Burt M., Fan, Xinyu, Redei, Eva E., Mulligan, Megan K., Chen, Hao
Format: Article
Language:English
Subjects:
Analgesics, Opioid - administration & dosage
Analgesics, Opioid - toxicity
Animals
Disease Models, Animal
Drug abuse
Female
Genetic Predisposition to Disease
heredity
Heritability
Inbreeding
Male
Narcotics
operant
Operant conditioning
Opioid-Related Disorders - genetics
Opioid-Related Disorders - physiopathology
Opioids
oral
Oxycodone
Oxycodone - administration & dosage
Oxycodone - toxicity
Pharmacokinetics
rat
Rats
Rats, Inbred Dahl
Rats, Inbred F344
Rats, Inbred Lew
Rats, Wistar
Self Administration
Sex
Sexes
strain
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Summary:The steady rise in prescription opioids such as oxycodone has led to a virulent epidemic of widespread abuse and deaths in the United States; approximately 80% of affected individuals initiate the habitual use of oxycodone by using prescription oral oxycodone. Given the importance of drug pharmacokinetics in determining abuse potential, we designed an oral operant oxycodone self‐administration (SA) procedure in rats to model drug intake by most human users/abusers of oxycodone. Key aspects of the model include limited initial drug intake followed by increasing drug concentrations during extended 4‐h sessions on alternating days. Sex and genetic predisposition are major determinants of human opiate abuse. Therefore, we studied females in seven inbred strains (WLI, WMI, LEW, DSS, F344, BN and SHR) and both sexes in three of these strains. All strains increased intake across serially increasing doses (0.025–0.2 mg/ml; p 
ISSN:1601-1848
1601-183X
DOI:10.1111/gbb.12770