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Previous studies have revealed that\n                    <jats:italic>Sulf1\/Sulf2<\/jats:italic>\n                    double knockout (KO) mice had defects in differentiation and axon guidance during development, but their functional roles in the adult brain remain largely unknown. We recently found that\n                    <jats:italic>Sulf1<\/jats:italic>\n                    mRNA is highly expressed in the nucleus accumbens (NAc) shell and that\n                    <jats:italic>Sulf1<\/jats:italic>\n                    expression is detected in both types of medium spiny neurons expressing dopamine D1 or D2 receptors. Moreover, we found that\n                    <jats:italic>Sulf1<\/jats:italic>\n                    KO led to changes in membrane excitability and excitatory synaptic transmission in medium spiny neurons of the NAc in adult mice. These findings suggest possible roles of\n                    <jats:italic>Sulf1<\/jats:italic>\n                    in the functions of NAc circuitry. To address this question, we performed behavioral tests using\n                    <jats:italic>Sulf1<\/jats:italic>\n                    KO mice. We found that constitutive\n                    <jats:italic>Sulf1<\/jats:italic>\n                    KO mice showed impairment in both the cocaine\u2010induced conditioned place preference (CPP) test and inhibitory avoidance (IA) test. Next, to examine which cell types the\n                    <jats:italic>Sulf1<\/jats:italic>\n                    gene is required for, we generated\n                    <jats:italic>Sulf1<\/jats:italic>\n                    floxed mice by means of CRISPR\u2010Cas9\u2010mediated genome editing and mated them with mice expressing Cre recombinase under a promoter for either the dopamine D1 or D2 receptor\u2010encoding genes.\n                    <jats:italic>Sulf1<\/jats:italic>\n                    conditional knockout (cKO) in cells expressing dopamine D1 receptors led to impairment only in the CPP test, whereas\n                    <jats:italic>Sulf1<\/jats:italic>\n                    cKO in D2 receptor\u2010expressing cells resulted in impairment only in the IA test. These results demonstrate that\n                    <jats:italic>Sulf1<\/jats:italic>\n                    is required for both reward and aversion learning, and that the D1\u2010 and D2\u2010pathways distinctly regulate these functions. The present study suggests that\n                    <jats:italic>Sulf1<\/jats:italic>\n                    is essential for neuronal functions and behavioral control in the adult brain.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70338-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70338","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T06:52:03Z","timestamp":1767595923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Essential Roles of Heparan Sulfate Endosulfatase Sulf1 in Reward and Aversion Learning Through Distinct Dopamine\n                    <scp>D1<\/scp>\n                    and\n                    <scp>D2<\/scp>\n                    Receptor Pathways in Male Mice"],"prefix":"10.1111","volume":"170","author":[{"given":"Ken","family":"Miya","sequence":"first","affiliation":[{"name":"Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"Department of Molecular Neurobiology, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent","family":"Ohta","sequence":"additional","affiliation":[{"name":"Laboratory for Advanced Brain Functions, Institute for Protein Research The University of Osaka  Suita Osaka Japan"},{"name":"Graduate School of Medicine The University of Osaka  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Keino\u2010Masu","sequence":"additional","affiliation":[{"name":"Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"Department of Molecular Neurobiology, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Okada","sequence":"additional","affiliation":[{"name":"Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"Department of Molecular Neurobiology, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiya","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Transborder Medical Research Center, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki 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