Effects of 2, 5-Dimethoxy-4-Methylamphetamine (DOM) and 2-Piperazin-1-yl-Quinoline (Quipazine) on Fentanyl Versus Food Choice in Rhesus Monkeys

There has been increasing interest in the potential therapeutic effects of drugs with agonist properties at serotonin 2A subtype (5-HT_2A) receptors (e.g., psychedelics), including treatment of substance use disorders. Studying interactions between 5-HT_2A receptor agonists and other drugs is important for understanding potential therapeutic effects as well as adverse interactions. Direct-acting 5-HT_2A receptor agonists such as 2, 5-dimethoxy-4-methylamphetamine (DOM) and 2-piperazin-1-yl-quinoline (quipazine) enhance some (e.g., antinociceptive) effects of opioids; however, it is unclear whether they alter the abuse-related effects of opioids. This study examined whether DOM and quipazine alter the reinforcing effects of fentanyl in rhesus monkeys (n = 6) responding under a food versus drug choice procedure. Responding on one lever delivered sucrose pellets and responding on the other lever delivered intravenous (i.v.) infusions. In one set of experiments, fentanyl (0.1-3.2 μg/kg/infusion) versus food choice sessions were preceded by noncontingent i.v. pretreatments with DOM (0032-0.32 mg/kg), quipazine (0.32-1.0 mg/kg), naltrexone (0.032 mg/kg), or heroin (0.1 mg/kg). In another set of experiments, fentanyl was available during choice sessions in combination with DOM (0.32-100 μg/kg/infusion) or quipazine (3.2-320 μg/kg/infusion) in varying dose ratios. Naltrexone decreased and heroin increased fentanyl choice, demonstrating sensitivity of responding to pharmacological manipulation. However, whether given as a pretreatment or made available in combination with fentanyl as a mixture, neither DOM nor quipazine significantly altered fentanyl choice. These results suggest that 5-HT_2A receptor agonists do not enhance the reinforcing effects of opioids and, thus, will not likely enhance abuse potential.