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During abstinence, oxycodone seeking progressively increases, a phenomenon termed incubation of oxycodone craving. We previously demonstrated a causal role of orbitofrontal cortex (OFC) in this incubation. Here, we studied the interaction between glutamatergic projections from OFC and dopamine 1\u2010family receptor (D1R) signaling in dorsal striatum (DS) in this incubation in male rats. We first examined the causal role of D1R signalling in DS in incubated oxycodone seeking. Next, we combined fluorescence\u2010conjugated cholera toxin subunit B (CTb\u2010555, a retrograde tracer) with Fos (a neuronal activity marker) to assess whether the activation of OFC\u2192DS projections was associated with incubated oxycodone seeking. We then used a pharmacological asymmetrical disconnection procedure to examine the role of the interaction between projections from OFC and D1R signalling in DS in incubated oxycodone seeking. We also tested the effect of unilateral pharmacological inactivation of OFC or unilateral D1R blockade of DS on incubated oxycodone seeking. Finally, we assessed whether contralateral disconnection of OFC\u2192DS projections impacted non\u2010incubated oxycodone seeking on abstinence day 1. We found that D1R blockade in DS decreased incubated oxycodone seeking and OFC\u2192DS projections were activated during incubated oxycodone seeking. Moreover, anatomical disconnection of OFC\u2192DS projections, but not unilateral inactivation of OFC or unilateral D1R blockade in DS, decreased incubated oxycodone seeking. Lastly, contralateral disconnection of OFC\u2192DS projections had no effect on oxycodone seeking on abstinence day 1. Together, these results demonstrated a causal role of OFC\u2192DS projections in incubation of oxycodone craving.<\/jats:p>","DOI":"10.1111\/adb.13440","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T02:03:43Z","timestamp":1728439423000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Orbitofrontal cortex to dorsal striatum circuit is critical for incubation of oxycodone craving after forced abstinence"],"prefix":"10.1111","volume":"29","author":[{"given":"Hongyu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Psychology University of Maryland College Park  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adedayo","family":"Olaniran","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Maryland College Park  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Maryland College Park  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Strauch","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Maryland College Park  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A. 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