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      Transcriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brain

      Jacobson, Gregory M.; Voss, Logan J.; Klockars, Anica; Bird, Steve; Dimitrov, Ivo; Denny, William A.; Olszewski, Pawel K.; Sleigh, James W.; Harvey, Martyn G.
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      2019 jacobson voss klockars bird et al BMC Genomics.pdf
      Published version, 2.181Mb
      DOI
       10.1186/s12864-019-5649-6
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      Jacobson, G. M., Voss, L. J., Klockars, A., Bird, S., Dimitrov, I., Denny, W. A., … Harvey, M. G. (2019). Transcriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brain. BMC GENOMICS, 20. https://doi.org/10.1186/s12864-019-5649-6
      Permanent Research Commons link: https://hdl.handle.net/10289/12585
      Abstract
      Background

      Ketamine ester analogs, SN 35210 and SN 35563, demonstrate different pharmacological profiles to ketamine in animal models. Both confer hypnosis with predictably rapid offset yet, paradoxically, SN35563 induces a prolonged anti-nociceptive state. To explore underlying mechanisms, broad transcriptome changes were measured and compared across four relevant target regions of the rat brain.

      Results

      SN 35563 produced large-scale alteration of gene expression in the Basolateral Amygdala (BLA) and Paraventricular Nucleus of the Thalamus (PVT), in excess of 10x that induced by ketamine and SN 35210. A smaller and quantitatively similar number of gene changes were observed in the Insula (INS) and Nucleus Accumbens (ACB) for all three agents. In the BLA and PVT, SN 35563 caused enrichment for gene pathways related to the function and structure of glutamatergic synapses in respect to: release of neurotransmitter, configuration of postsynaptic AMPA receptors, and the underlying cytoskeletal scaffolding and alignment.

      Conclusion

      The analgesic ketamine ester analog SN 35563 induces profound large-scale changes in gene expression in key pain-related brain regions reflecting its unique prolonged pharmacodynamic profile.
      Date
      2019
      Type
      Journal Article
      Publisher
      BMC
      Rights
      © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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