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Oral prescription opioid-seeking behavior in male and female mice.
Addict Biol 2019; :e12828AB

Abstract

A significant portion of prescription opioid users self-administer orally rather than intravenously. Animal models of opioid addiction have demonstrated that intravenous cues are sufficient to cause drug seeking. However, intravenous models may not characterize oral users, and the preference to self-administer orally appears to be partially influenced by the user's sex. Our objectives were to determine whether oral opioid-associated cues are sufficient for relapse and whether sex differences exist in relapse susceptibility. Mice orally self-administered escalating doses of oxycodone under postprandial (prefed) or non-postprandial (no prefeeding) conditions. Both sexes demonstrated cue-induced reinstatement following abstinence. In separate mice, we found that oral oxycodone cues were sufficient to reinstate extinguished oral oxycodone-seeking behavior following abstinence without prior postprandial or water self-administration training. During self-administration, we incidentally found that female mice earned significantly more mg/kg oxycodone than male mice. Follow-up studies indicated sex differences in psychomotor stimulation and plasma oxycodone/oxymorphone following oral oxycodone administration. In addition, gonadal studies were performed in which we found divergent responses where ovariectomy-enhanced and orchiectomy-suppressed oral self-administration. While the suppressive effects of orchiectomy were identified across doses and postprandial conditions, the enhancing effects of ovariectomy were selective to non-postprandial conditions. These studies establish that (a) oral drug cues are sufficient to cause reinstatement that is independent of prandial conditions and water-seeking behavior, (b) earned oral oxycodone is larger in female mice compared with male mice potentially through differences in psychomotor stimulation and drug metabolism, and (c) gonadectomy produces divergent effects on oral oxycodone self-administration between sexes.

Authors+Show Affiliations

Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA.Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA.Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA.Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA.Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA.Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA.Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA.Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31489746

Citation

Phillips, Alysabeth G., et al. "Oral Prescription Opioid-seeking Behavior in Male and Female Mice." Addiction Biology, 2019, pp. e12828.
Phillips AG, McGovern DJ, Lee S, et al. Oral prescription opioid-seeking behavior in male and female mice. Addict Biol. 2019.
Phillips, A. G., McGovern, D. J., Lee, S., Ro, K., Huynh, D. T., Elvig, S. K., ... Root, D. H. (2019). Oral prescription opioid-seeking behavior in male and female mice. Addiction Biology, pp. e12828. doi:10.1111/adb.12828.
Phillips AG, et al. Oral Prescription Opioid-seeking Behavior in Male and Female Mice. Addict Biol. 2019 Sep 5;e12828. PubMed PMID: 31489746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral prescription opioid-seeking behavior in male and female mice. AU - Phillips,Alysabeth G, AU - McGovern,Dillon J, AU - Lee,Soo, AU - Ro,Kyu, AU - Huynh,David T, AU - Elvig,Sophie K, AU - Fegan,Katelynn N, AU - Root,David H, Y1 - 2019/09/05/ PY - 2019/04/26/received PY - 2019/08/15/revised PY - 2019/08/16/accepted PY - 2019/9/7/entrez PY - 2019/9/7/pubmed PY - 2019/9/7/medline KW - opioid KW - oxycodone KW - relapse KW - sex differences SP - e12828 EP - e12828 JF - Addiction biology JO - Addict Biol N2 - A significant portion of prescription opioid users self-administer orally rather than intravenously. Animal models of opioid addiction have demonstrated that intravenous cues are sufficient to cause drug seeking. However, intravenous models may not characterize oral users, and the preference to self-administer orally appears to be partially influenced by the user's sex. Our objectives were to determine whether oral opioid-associated cues are sufficient for relapse and whether sex differences exist in relapse susceptibility. Mice orally self-administered escalating doses of oxycodone under postprandial (prefed) or non-postprandial (no prefeeding) conditions. Both sexes demonstrated cue-induced reinstatement following abstinence. In separate mice, we found that oral oxycodone cues were sufficient to reinstate extinguished oral oxycodone-seeking behavior following abstinence without prior postprandial or water self-administration training. During self-administration, we incidentally found that female mice earned significantly more mg/kg oxycodone than male mice. Follow-up studies indicated sex differences in psychomotor stimulation and plasma oxycodone/oxymorphone following oral oxycodone administration. In addition, gonadal studies were performed in which we found divergent responses where ovariectomy-enhanced and orchiectomy-suppressed oral self-administration. While the suppressive effects of orchiectomy were identified across doses and postprandial conditions, the enhancing effects of ovariectomy were selective to non-postprandial conditions. These studies establish that (a) oral drug cues are sufficient to cause reinstatement that is independent of prandial conditions and water-seeking behavior, (b) earned oral oxycodone is larger in female mice compared with male mice potentially through differences in psychomotor stimulation and drug metabolism, and (c) gonadectomy produces divergent effects on oral oxycodone self-administration between sexes. SN - 1369-1600 UR - https://www.unboundmedicine.com/medline/citation/31489746/Oral_prescription_opioid-seeking_behavior_in_male_and_female_mice L2 - https://doi.org/10.1111/adb.12828 DB - PRIME DP - Unbound Medicine ER -