Oxycodone and VK4-116 Dosing Protocol

Oxycodone (Sigma Aldrich, St. Louis, MO, USA) was dissolved in 0.9% sodium chloride (Hospira, Lake Forest, IL, USA) and administered at a dose of 150 μg/0.1 ml/kg. The dose of Oxycodone was selected based on previous studies (Wade et al., 2015 (link); Nguyen et al., 2019 (link)) and because it produces significant plasma Oxycodone concentrations (40 ng/ml; Mavrikaki et al., 2017 (link)). VK4-116 was synthesized by Kumar et al. (2016 (link)) in the Newman laboratory at the National Institute on Drug Abuse, based on a published procedure. VK4-116 was dissolved in 25% 2-hydroxypropyl-β-cyclodextrin and intraperitoneally injected at doses of 0, 5, 15, and 25 mg/kg as previously reported (You et al., 2019 (link)).