Oxycodone self-administration and withdrawal behaviors in male and female Wistar rats

Adam Kimbrough, Jenni Kononoff, Sierra Simpson, Marsida Kallupi, Sharona Sedighim, Kenia Palomino, Dana Conlisk, Jeremiah D. Momper, Giordano de Guglielmo, Olivier George
Psychopharmacology. 2020-02-29; 237(5): 1545-1555
DOI: 10.1007/s00213-020-05479-y

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Kimbrough A(1), Kononoff J(2), Simpson S(1)(2), Kallupi M(1), Sedighim S(1), Palomino K(3), Conlisk D(2), Momper JD(3), de Guglielmo G(1), George O(4).

Author information:
(1)Department of Psychiatry, School of Medicine, University of California San
Diego, 9500 Gilman Drive, MC 0714, La Jolla, CA, 92093-0737, USA.
(2)Department of Neuroscience, The Scripps Research Institute, La Jolla, CA,
92037, USA.
(3)Skaggs School of Pharmacy and Pharmaceutical Sciences, University of
California San Diego, La Jolla, CA, 92093, USA.
(4)Department of Psychiatry, School of Medicine, University of California San
Diego, 9500 Gilman Drive, MC 0714, La Jolla, CA, 92093-0737, USA.
.

RATIONALE: Over the last decade, oxycodone has become one of the most widely
abused drugs in the USA. Oxycodone use disorder (OUD) is a serious health problem
that has prompted a need to develop animal models of OUD that have both face and
predictive validity. Oxycodone use in humans is more prevalent in women and leads
to pronounced hyperalgesia and irritability during withdrawal. However, unclear
is whether current animal models of oxycodone self-administration recapitulate
these characteristics in humans.
OBJECTIVES: We assessed the face validity of a model of extended-access oxycodone
self-administration in rats by examining the escalation of oxycodone intake and
behavioral symptoms of withdrawal, including irritability-like behavior and
mechanical nociception, in male and female Wistar rats.
RESULTS: Both male and female rats escalated their oxycodone intake over fourteen
12-h self-administration sessions. After escalation, female rats administered
more drug than male rats. No differences in plasma oxycodone levels were
identified, but males had a significantly higher level of oxycodone in the brain
at 30 min. Extended access to oxycodone significantly decreased aggressive-like
behavior and increased defensive-like behaviors when tested immediately after a
12-h self-administration session, followed by a rebound increase in
aggressive-like behavior 12 h into withdrawal. Tests of mechanical nociception
thresholds during withdrawal indicated pronounced hyperalgesia. No sex
differences in irritability-like behavior or pain sensitivity were observed.
CONCLUSIONS: The present study demonstrated the face validity of the extended
access model of oxycodone self-administration by identifying sex differences in
the escalation of oxycodone intake and pronounced changes in pain and affective
states.

Auteurs Bordeaux Neurocampus