“A Method for Touchscreen‐Based Oral Self‐Administration of Oxycodone in Mice”

Abstract

BackgroundOpioid use disorder (OUD) is a significant public health concern and there is a critical need for new therapeutic options. Prescription opioids, which are most often taken orally, make up a large percentage of opioids abused. Preclinical assays that model oral opioid‐seeking and ‐taking allow us to study neurobiological circuits that may be involved in OUD and identify factors that exacerbate or decrease risk. Behavioral assays that incorporate oral opioid consumption have been developed and provide a valuable addition to the OUD model toolbox where they complement intravenous administration models. Here, we describe a novel, touchscreen‐based mouse model of oral oxycodone (OXY) administration.ObjectiveOur goal was to develop and implement a touchscreen‐based assay of oral self‐administration (SA) of OXY.MethodsAll mice were food restricted to 85‐90% of their free‐feeding weight before the start of testing. The training stage consisted of a postprandial phase, during which mice received a one‐hour pre‐session prior to being placed in the touchscreen chambers. During the pre‐session, mice were given their daily food allotment, with no access to water. Mice were then placed in the touchscreen chambers for 90 min SA sessions. They began with water SA on an FR1 schedule, and once they met criteria (10 active touches), they progressed to water SA on an FR2 schedule, for 3 days. Mice were then introduced to increasing concentrations of OXY HCl solution (0, 0.05, 0.10, 0.30, 0.50, and 1.00 mg/ml), which they self‐administered for 3 days each. After access to the 1.00 mg/ml concentration for 3 days, mice were then given access to this concentration for 7 days where the pre‐session included no food and unlimited access to water (non‐postprandial phase).HypothesisOur hypothesis was that both male and female mice would be able to acquire OXY SA at the increasing concentrations, as well as be able to maintain SA at the highest concentration under non‐postprandial conditions. Based on prior literature, we hypothesize that female mice would show greater SA of OXY than males.ResultsMale and female mice learned to self‐administer water under postprandial conditions and continued to seek and consume rewards when OXY was introduced. As the concentration of OXY increased, total consumption of fluid decreased but the amount of OXY consumed (mg/kg) increased across both males and females. At the two lowest OXY concentrations (0.05, 0.10 mg/ml), males earned significantly more rewards than female mice (p=0.001 and p=0.016, respectively). However, when we accounted for the weight of the mice, total amount of OXY consumed (mg/kg) was no different between males and females. Additionally, both male and female mice maintained OXY SA at the highest concentration, under non‐postprandial conditions.ConclusionOur study thus indicates that male and female mice can acquire OXY SA under this paradigm, in touchscreen chambers. Further, we found that males earned more OXY rewards at the lowest two OXY concentrations. However, when differences in body weight are considered, males and females consume similar amounts of OXY. Our current dataset confirms the utility of our touchscreen‐based OXY SA model.