Sex differences in responsiveness to the prescription opioid oxycodone in mice.
Over-prescription and increased nonmedical use of oxycodone has become a major concern. Despite its increased use, preclinical data concerning oxycodone's effects are still limited, especially in rodent models. To address this, we examined oxycodone's effects on place preference, locomotor activation, corticosterone levels, and thermal analgesia across a range of doses (between 0.3 and 10mg/kg) in gonadally intact, adult male and female C57BL/6J mice. Males and females showed oxycodone-induced conditioned place preference and did not show significant between-sex differences in their place preference behavior. During both CPP conditioning sessions and open field assay, locomotor activity was increased by 1, 3, and 10mg/kg oxycodone in females and by 3 and 10mg/kg oxycodone in males. Plasma corticosterone levels were higher in females (compared to males) at baseline as well as following acute oxycodone injection and open field testing. The time course of oxycodone-induced analgesia was similar in males and females, however the total antinociceptive effect (AUC0-120min) was larger in males compared to females at the highest dose tested (10mg/kg). Taken together, these data suggest that male and female mice are modestly different in their responses to oxycodone.
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States. Electronic address: dcollins@rockefeller.edu.
Devon
D
Collins
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
Brian
B
Reed
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
Yong
Y
Zhang
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
Mary Jeanne
MJ
Kreek
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010098:Oxycodone / Q000494:pharmacology*; D012727:Sex Characteristics
D000701:Analgesics, Opioid; D010098:Oxycodone; D051544:Cytochrome P-450 CYP3A; D003345:Corticosterone
Antinociception; Conditioned place preference; Corticosterone; Locomotor behavior; Oxycodone; Sex difference