Summary Abstract Heroin use disorder continues to be a serious and growing national health problem that requires an effective solution that produces long-term abstinence and prevents relapse. Agonist replacement pharmacotherapies show promise but continue to fall short of being highly effective when the goal is long-term abstinence and relapse prevention. Research shows that behavioral treatment strategies can be successful in maintaining abstinence and preventing relapse. However, most behavioral strategies are focused on learning new responses to drug and drug stimuli that are not maintained for significant periods of time after treatment; when the new learning conditions are stopped or the user returns to the original drug contexts there is relapse. Given these limitations the development of more effective strategies is warranted. Environmental enrichment (EE) is a strategy that is not dependent on learning new responses to drug or drug stimuli and therefore may not be prone to the limitations mentioned above. We have proposed that EE is a novel strategy that can effectively treat heroin addiction by facilitating abstinence and protecting against relapse. Our preliminary data has shown that EE can facilitate abstinence from heroin and reduce cue-induced relapse in animal models. Although these findings are extremely promising there is critical knowledge still missing which will be addressed here. This proposal is aimed at (1) testing the effects of EE as a treatment for heroin addiction in females (which to date has not been done), across different periods of craving incubation and in animals with extended access to heroin self-administration (a drug-taking model that leads to escalated drug intake thought to represent the same escalation seen in addicted individuals) and (2) investigating the neural mechanisms by which EE is effective in facilitating abstinence and reducing relapse. If the proposed aims demonstrate that EE facilitates abstinence and diminishes the capacity of heroin cues to induce relapse in males and females, across long periods of craving incubation (i.e., withdrawal) and with extended access to drug it will significantly widen the spectrum of behavioral strategies that can be used as treatments for heroin addiction. Also, if the proposed aims show that EE reduces the capacity of heroin cues to activate mesocorticolimbic regions then they will begin to shed light on the neurobiological mechanisms though which EE has its beneficial effects on heroin (or other) substance use disorder. The results of these studies will provide important data that can be used to further refine treatment strategies for heroin (and other drug) use disorder.