{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:17:53Z","timestamp":1785453473445,"version":"3.56.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1MH51290-18"],"award-info":[{"award-number":["RO1MH51290-18"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA031231 K01"],"award-info":[{"award-number":["DA031231 K01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The high comorbidity between schizophrenia and cigarette smoking points to a possible shared heritable factor predisposing individuals with schizophrenia to nicotine addiction. The N-methyl-d-aspartate (NMDA) receptor has been highly implicated in both schizophrenia and nicotine addiction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In the present study, we used mice with a null mutation on the serine racemase gene (srr), an established risk gene for schizophrenia, which encodes the enzyme to produce the NMDA receptor co-agonist d-serine, to model the pathology of schizophrenia and to determine whether NMDA receptor hypofunction reduced the ability of srr\u2212\/\u2212 mice to identify nicotine\u2019s subjective effects. Established nicotine discrimination procedures were used to train srr\u2212\/\u2212 and wild-type (WT) mice to discriminate 0.4 mg\/kg nicotine under a 10-response fixed-ratio (FR10) schedule of food reinforcement.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Results show that WT mice reliably acquired 0.4 mg\/kg nicotine discrimination in about 54 training sessions, whereas srr\u2212\/\u2212 mice failed to acquire robust 0.4 mg\/kg nicotine discrimination even after extended (&amp;gt;70) training sessions. These results show that NDMA receptor hypofunction in srr\u2212\/\u2212 mice decreased sensitivity to the interoceptive effects of nicotine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Projected to humans, NMDA receptor hypofunction caused by mutations to the serine racemase gene in schizophrenia may reduce sensitivity to nicotine\u2019s subjective effects leading to increased nicotine consumption to produce the same effects as those unaffected by schizophrenia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications<\/jats:title>\n                  <jats:p>There is high comorbidity between schizophrenia and nicotine dependence as well as possible shared genetic risk factors between the two. The serine racemase knockout mouse (srr\u2212\/\u2212) with NMDA receptor hypofunction has been developed as a model for schizophrenia. We found that srr\u2212\/\u2212 mice were unable to acquire 0.4 mg\/kg nicotine discrimination, while WT mice readily discriminated nicotine. These results show that decreased NMDA receptor function present in srr\u2212\/\u2212 mice and patients with schizophrenia may result in reduced sensitivity to nicotine\u2019s interoceptive effects, leading to increased nicotine consumption to produce the same subjective effects as those unaffected by schizophrenia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ntr\/ntae156","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T22:03:03Z","timestamp":1719266583000},"page":"1744-1748","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Serine Racemase Deletion on Nicotine Discrimination"],"prefix":"10.1093","volume":"26","author":[{"given":"Isabel L","family":"Yu","sequence":"first","affiliation":[{"name":"Harvard Medical School Department of Psychiatry, , Boston, MA,","place":["USA"]},{"name":"McLean Hospital Behavioral Biology Program, Integrative Neurochemistry Laboratory, , Belmont, 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