The orexin/hypocretin system is involved in several addiction-related behaviors. In the present experiments, we examined the involvement of orexin in heroin reinforcement and relapse by administering the orexin 1 receptor antagonist SB-334867 prior to heroin self-administration or prior to cue-induced or heroin-induced reinstatement of extinguished heroin seeking in male Sprague Dawley rats. SB-334867 (30 mg/kg, intraperitoneal) reduced heroin intake during self-administration under fixed ratio-1 and progressive ratio schedules. SB-334867 also attenuated reinstatement of heroin seeking elicited by cues, but not reinstatement elicited by a heroin prime. These results indicate that orexin antagonism reduces heroin self-administration, and they support a role for orexin in cue-triggered drug relapse.
