Cannabinoid Receptor Modulators in Cisplatin-Induced Nausea

Delta-9-tetrahydrocannabinol (∆⁹-THC) was obtained from the National Institute on Drug Abuse Drug Supply Program (Bethesda, MD, United States). The selective CB₁ receptor inverse agonist rimonabant (SR141716; Rinaldi-Carmona et al., 1994 (link)), and the CB₂ receptor-selective inverse agonist, SR144528 (Rinaldi-Carmona et al., 1998 (link)), were obtained from the Cayman Chemical Company (Ann Arbor, MI, United States). For all experiments, ∆⁹-THC, rimonabant, and SR144528 were dissolved in 0.9% saline, 5% Cremaphor EL, and 5% ethanol (18:1:1 v/v/v) and administered intraperitoneally (IP) using an injection volume of 10 ml/kg. Drug injections were given either 30 or 60 min (see below) prior to testing. Cisplatin was obtained from Tocris (Minneapolis, MN, United States), dissolved in 0.9% physiological saline, and administered IP immediately following subcutaneous (SC) administration of 1 ml of 4% sodium bicarbonate (Fisher Scientific, Pittsburgh, PA, United States) solution dissolved in 0.9% saline. The selection of Δ⁹-THC, rimonabant, and SR144528 doses were based on prior work in our lab (Yuill et al., 2017 (link); Henderson-Redmond et al., 2020 (link)).