In 2023, 28.9 million Americans aged 12 or older qualified as having alcohol use disorder (AUD) (American Psychiatric Association, 2022; SAMHSA, 2023). There are limited approved pharmacotherapies for AUD (Burnette et al., 2022), and those available do not work for all patients, highlighting the need for novel pharmacotherapies. Preclinical models have implicated the orexin system as a potential target for modifying alcohol-related behaviors. Selective and dual antagonism of orexin-1 and orexin-2 receptors (OX1 and OX2) has been shown to reduce alcohol seeking and intake in rodents (Anderson et al., 2014, Barson et al., 2015, Burnette et al., 2022, Jupp et al., 2011, Lawrence et al., 2006, Lei et al., 2019, Srinivasan et al., 2012). Suvorexant is a dual-orexin receptor antagonist that is FDA approved for the treatment of insomnia and has gained interest for its potential as a treatment for AUD (Burnette et al., 2022, Campbell et al., 2020a; Campbell, et al., 2020b; Flores-Ramirez et al., 2022). A case report of an individual who had comorbid AUD and insomnia also showed that suvorexant treatment yielded reductions in alcohol craving suggesting clinical utility (Campbell et al., 2024). Suvorexant itself is generally safe, and preclinical data indicates that it does not produce withdrawal symptoms or have reinforcing effects on its own (Born et al., 2017).

Nonhuman primate models of alcohol self-administration provide a key translational link between rodent studies to human pharmacotherapy trials for AUD. Baboons are a particularly valuable model as they demonstrate similar alcohol metabolism and pharmacokinetic parameters to humans (Fridman and Popova, 1988, Jolivette and Ward, 2005). The current study used baboons that had an extensive history of alcohol drinking and evaluated alcohol self-administration behavior under a chained schedule of reinforcement (CSR) procedure (Kaminski et al., 2008, Weerts et al., 2006). The CSR procedure allows for the examination of drug effects on alcohol seeking responses maintained by conditioned reinforcement in the presence of alcohol-related cues, as well as alcohol self-administration and consumption, all within a single session. The CSR procedure is sensitive to the magnitude of the reinforcer and the duration of abstinence, and is responsive to medications that have demonstrated a significant reduction of alcohol consumption in human studies (e.g., varenicline, baclofen, and naltrexone) (Duke et al., 2014, Holtyn et al., 2017, Holtyn and Weerts, 2019, Kaminski et al., 2012, Kaminski et al., 2013, Kaminski and Weerts, 2014, Lee et al., 2024, Moore et al., 2023). Further, this procedure results in high levels of alcohol self-administration (~1.0 g/kg per day) and blood alcohol levels in excess of 0.08 % (Holtyn et al., 2014, Holtyn et al., 2017, Kaminski et al., 2008, Moore et al., 2023). The present study used the CSR procedure to evaluate the effects of acute suvorexant treatment on alcohol seeking and self-administration.