Suvorexant, an orexin/hypocretin receptor antagonist, attenuates motivational and hedonic properties of cocaine

• DOI: 10.1111/adb.12507
• Publication Date: 2017-04-17T11:42:39Z
• Authors: Taylor A. Gentile; Steven J. Simmons; David J. Barker; Jessica K. Shaw; Rodrigo A. España; John W. Muschamp
• Keywords: Orexin receptor; Orexin-A

Abstract Orexins (‘hypocretins’) are peptides produced by neurons of the hypothalamus that project to structures implicated in reward and emotion processing. Converging evidence demonstrates functional roles orexin signaling arousal, sleep/wakefulness motivated behaviors for natural drug rewards. Suvorexant, a dual receptor antagonist, recently received approval from US Food Drug Administration treat insomnia. In Experiment 1, rats self‐administered cocaine under progressive‐ratio schedule reinforcement effects suvorexant on motivation self‐administer were measured. 2, assessed using place conditioning paradigm, 50‐kHz ultrasonic vocalizations also recorded track changes hedonic reactivity cocaine. To rule out potentially confounding suvorexant‐induced somnolence, locomotor activity was 3, cocaine‐evoked elevations ventral striatal dopamine examined. Data reveal (i) reduced number infusions earned during self‐administration; (ii) attenuated initial positive prevented preference; (iii) did not affect cocaine‐induced hyperlocomotion (iv) extracellular dopamine. The present study examined therapeutic potential rodent models use disorder. These results contribute toward growing literature supporting antagonists treating substance disorders.