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The poor long‐term success of fear extinction‐based exposure therapy for post‐traumatic stress disorder (PTSD) is often caused by the relapse of previously extinguished fear. We have previously observed that activation of substantia nigra (SN) dopamine (DA) neurons during fear extinction enhances extinction memory and reduces renewal. Although the specific targets mediating the effects of SN DA on extinction are unknown, their identification could pave the way for the development of novel strategies to reduce fear relapse in PTSD patients. A primary target of SN DA is the dorsal striatum, which consists of two regions: The dorsomedial striatum (DMS), responsible for goal directed learning, and the dorsolateral striatum (DLS), concerning more inflexible, habitual behaviors. The goal of these experiments was to begin to investigate the roles of the DMS and DLS in fear extinction and relapse in adult, male Long Evans rats. Inactivation of the DLS during auditory fear extinction with a Muscimol/Baclofen cocktail (0.03/0.3 nmol/uL) enhanced fear extinction memory but had no effect on fear renewal, while inactivation of the DMS prevented renewal, but had no effect on extinction memory in the extinction context. To investigate the involvement of DA, D1 receptor signaling was blocked in either the DMS or DLS during fear extinction. D1 blockade in the DMS impaired extinction retrieval in the extinction context, but the extinction memory remained susceptible to renewal. D1 blockade in the DLS had no effect on extinction memory or renewal. Despite this, optogenetic stimulation of SN terminals in the DLS during fear extinction reduced fear renewal without impacting extinction memory in the extinction context. These results suggest that the DMS and DLS play different roles in fear extinction and relapse. The DMS supports context‐specific fear extinction through a mechanism involving D1 receptor signaling. Although the contribution of the DLS to normal fear extinction is minimal, fear extinction memory can be rendered resistant to renewal by manipulations that increase the role of the DLS in extinction (DMS inactivation, optogenetic stimulation). Manipulations that increase the involvement of the DLS in fear extinction, such as exercise, could therefore represent effective augmentation strategies for fear extinction in order to reduce relapse.Support or Funding InformationNIH grant 068283 NIH grant 2 T34 GM096958‐06This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.