ArticleNicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco2024
Impact of Serine Racemase Deletion on Nicotine Discrimination.
Article in Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- D-serine: A Multitalented Neuromodulator in Brain Function, Systemic Homeostasis, and Disease.Cellular and molecular neurobiology · 2026Review
- Research on Precision Medicine AI Algorithm for Neuro Immune Gastrointestinal Diseases based on Quantum Biochemistry and Computational Cancer Genetics.Current pharmaceutical biotechnology · 2026Article
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Abstract
introductionThe 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.
methodsIn 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-/- mice to identify nicotine's subjective effects. Established nicotine discrimination procedures were used to train srr-/- and wild-type (WT) mice to discriminate 0.4 mg/kg nicotine under a 10-response fixed-ratio (FR10) schedule of food reinforcement.
resultsResults show that WT mice reliably acquired 0.4 mg/kg nicotine discrimination in about 54 training sessions, whereas srr-/- mice failed to acquire robust 0.4 mg/kg nicotine discrimination even after extended (>70) training sessions. These results show that NDMA receptor hypofunction in srr-/- mice decreased sensitivity to the interoceptive effects of nicotine.
conclusionsProjected to humans, NMDA receptor hypofunction caused by mutations to the serine racemase gene in schizophrenia may reduce sensitivity to nicotine's subjective effects leading to increased nicotine consumption to produce the same effects as those unaffected by schizophrenia. IMPLICATIONS: 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-/-) with NMDA receptor hypofunction has been developed as a model for schizophrenia. We found that srr-/- 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-/- mice and patients with schizophrenia may result in reduced sensitivity to nicotine's interoceptive effects, leading to increased nicotine consumption to produce the same subjective effects as those unaffected by schizophrenia.
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