Mean (± SEM) reinstatement active responses induced by (A) METH-related cues or (B) METH injections (1 mg/kg, ip). (A) There were no significant age or sex differences in the attenuation of cue-induced reinstatement by orexin receptor antagonism. Both the selective OX1 receptor antagonist SB-334867 (vs. VEH/cue, # p < 0.05) and the selective OX2 receptor antagonist TCS-OX2-29 (vs. VEH/cue, ### p < 0.001) reduced reinstatement responding in adolescent and adult males and females. (B) Regardless of sex, SB-334867 suppressed METH-induced reinstatement selectively in adolescents (vs. VEH/cue, # p < 0.05; vs. adults, * p < 0.05), and TCS-OX2-29 suppressed reinstatement selectively in adults (vs. VEH/cue, # p < 0.05; vs. adolescents, ** p < 0.01). Group numbers: adol male = 7, adol female = 9–10, adult male = 7–8, adult female = 9.