Context-induced reinstatement of ethanol seeking. Rats were trained to respond for EtOH in two separate groups in similar operant chambers located in two distinct lab rooms, to provide different contexts. There were no behavioral differences between groups in terms of self-administration, extinction or reinstatement behavior. (A) Animals exhibited a strong preference for responding on the active lever (versus the inactive lever) during self-administration (left). Lever responding was then extinguished in the opposite room (middle). On test day, animals were returned to the room in which they originally learned to respond for EtOH, resulting in a significant reinstatement of responding on the active lever only (right). (B) There was significant variability in reinstatement behavior (active lever responding) as a result of returning to the original self-administration context. (C–D) Responding on the active lever during context-induced reinstatement was significantly, and positively, correlated with the percentage of Fos-positive orexin neurons in DMH (C) and LH (E), but not the PF (D). (F–H) Activation of orexin neurons was not correlated with the number of non-rewarded well entries animals made throughout the reinstatement session, a measure of non-goal-directed locomotor activity. *** p<0.001.