دورية أكاديمية
Classification of psychedelic drugs based on brain-wide imaging of cellular c-Fos expression.
| العنوان: | Classification of psychedelic drugs based on brain-wide imaging of cellular c-Fos expression. |
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| المؤلفون: | Aboharb F; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.; Weill Cornell Medicine/Rockefeller/Sloan-Kettering Tri-Institutional MD/PhD Program, New York, NY, 10021, USA., Davoudian PA; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.; Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, 06511, USA.; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT, 06511, USA., Shao LX; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA., Liao C; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.; Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, 06511, USA., Rzepka GN; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA., Wojtasiewicz C; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA., Dibbs M; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA., Rondeau J; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA., Sherwood AM; Usona Institute, Fitchburg, WI, 53711, USA., Kaye AP; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA.; Clinical Neurosciences Division, VA National Center for PTSD, West Haven, CT, 06477, USA.; Wu Tsai Institute, Yale University, New Haven, CT, 06511, USA., Kwan AC; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.; Department of Psychiatry, Weill Cornell Medicine, New York, NY, 10065, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 May 26. Date of Electronic Publication: 2024 May 26. |
| نوع المنشور: | Journal Article; Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in native brain tissues. We therefore developed a pipeline for drug classification using light sheet fluorescence microscopy of immediate early gene expression at cellular resolution followed by machine learning. We tested male and female mice with a panel of drugs, including psilocybin, ketamine, 5-MeO-DMT, 6-fluoro-DET, MDMA, acute fluoxetine, chronic fluoxetine, and vehicle. In one-versus-rest classification, the exact drug was identified with 67% accuracy, significantly above the chance level of 12.5%. In one-versus-one classifications, psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with >95% accuracy. We used Shapley additive explanation to pinpoint the brain regions driving the machine learning predictions. Our results support a novel approach for screening psychoactive drugs with psychedelic properties. Competing Interests: Competing interests A.C.K. has served as a scientific advisor for Empyrean Neuroscience, Freedom Biosciences, and Psylo. A.C.K. has received research support from Intra-Cellular Therapies. A.P.K has received research support from Transcend Therapeutics and Freedom Biosciences. A.P.K. has a provisional patent application related to psychedelics. The other authors report no financial relationships with commercial interests. |
| معلومات مُعتمدة: | T32 NS041228 United States NS NINDS NIH HHS; R01 MH121848 United States MH NIMH NIH HHS; R01 MH128217 United States MH NIMH NIH HHS; F30 DA059437 United States DA NIDA NIH HHS; T32 GM007205 United States GM NIGMS NIH HHS; K08 MH122733 United States MH NIMH NIH HHS |
| فهرسة مساهمة: | Keywords: MDMA; Psilocybin; antidepressant; drug discovery; entactogen; immediate early gene; ketamine; neural plasticity |
| تواريخ الأحداث: | Date Created: 20240603 Latest Revision: 20240610 |
| رمز التحديث: | 20240610 |
| مُعرف محوري في PubMed: | PMC11142187 |
| DOI: | 10.1101/2024.05.23.590306 |
| PMID: | 38826215 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2024.05.23.590306 |
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