Orexin / hypocretin 1 receptor antagonist reduces heroin self‐administration and cue‐induced heroin seeking

Abstract

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.