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Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system
Ketamine is a multifunctional drug with clinical applications as an anesthetic, pain management medication, and a fast-acting antidepressant. However, it is also recreationally abused for its dissociative effects. Recent studies in rodents are revealing the neuronal mechanisms mediating its actions,...
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| Published in: | Cell reports (Cambridge) 2023-12, Vol.42 (12), p.113491-113491, Article 113491 |
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| container_end_page | 113491 |
| container_issue | 12 |
| container_start_page | 113491 |
| container_title | Cell reports (Cambridge) |
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| creator | Datta, Malika S. Chen, Yannan Chauhan, Shradha Zhang, Jing De La Cruz, Estanislao Daniel Gong, Cheng Tomer, Raju |
| description | Ketamine is a multifunctional drug with clinical applications as an anesthetic, pain management medication, and a fast-acting antidepressant. However, it is also recreationally abused for its dissociative effects. Recent studies in rodents are revealing the neuronal mechanisms mediating its actions, but the impact of prolonged exposure to ketamine on brain-wide networks remains less understood. Here, we develop a sub-cellular resolution whole-brain phenotyping approach and utilize it in male mice to show that repeated ketamine administration leads to a dose-dependent decrease in dopamine neurons in midbrain regions linked to behavioral states, alongside an increase in the hypothalamus. Additionally, diverse changes are observed in long-range innervations of the prefrontal cortex, striatum, and sensory areas. Furthermore, the data support a role for post-transcriptional regulation in enabling ketamine-induced neural plasticity. Through an unbiased, high-resolution whole-brain analysis, this study provides important insights into how chronic ketamine exposure reshapes brain-wide networks.
[Display omitted]
•Whole-brain mapping of chronic ketamine-induced sub-cellular plasticity in dopamine system•Dose-dependent divergent changes in midbrain and hypothalamic dopamine domains•Divergently altered innervation of prefrontal, striatum, and sensory cortices•Data supporting post-transcriptional regulation of ketamine-induced structural plasticity
Datta et al. develop and use a whole-brain approach to reveal the impact of repeated ketamine exposure on the dopamine system. Findings also support post-transcriptional regulation of ketamine-induced neural network plasticity. This study provides crucial insights into how pharmacological agents like ketamine can reshape brain-wide networks in a non-uniform manner. |
| doi_str_mv | 10.1016/j.celrep.2023.113491 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10843582</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2211124723015036</els_id><sourcerecordid>2898954010</sourcerecordid><originalsourceid>FETCH-LOGICAL-c464t-d97a7a7c8e7c98d9c159cca4f77cb07264d426f2082ed5e90f81c26432f3560c3</originalsourceid><addsrcrecordid>eNp9UctOwzAQtBCIVqV_gFCOXFJsx0nsCwhVvKRKHABxtFxn07okcbDTSv17XKVU5YL3YHt3Zna1g9AlwROCSXazmmioHLQTimkyISRhgpygIaWExISy_PToPUBj71c4nAwTItg5GiQcp7v6EL19Lm0F8dwp00S1alvTLCIHG1CVj7olRIXZgFtA00WmbpXuIltGX9Cp2jQQ2abH2Lb_-63voL5AZ2Wgw3h_j9DH48P79DmevT69TO9nsWYZ6-JC5CqE5pBrwQuhSSq0VqzMcz3HOc1YwWhWUswpFCkIXHKiQzahZZJmWCcjdNfrtut5DYUOQzpVydaZWrmttMrIv5XGLOXCbiTBnCUpp0Hheq_g7PcafCdr48NmK9WAXXtJueAiZZjgAGU9VDvrvYPy0IdgufNErmTvidx5IntPAu3qeMYD6deBALjtARA2tTHgpNcGGg2FcaA7WVjzf4cfX1-f7A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2898954010</pqid></control><display><type>article</type><title>Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system</title><source>BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS</source><creator>Datta, Malika S. ; Chen, Yannan ; Chauhan, Shradha ; Zhang, Jing ; De La Cruz, Estanislao Daniel ; Gong, Cheng ; Tomer, Raju</creator><creatorcontrib>Datta, Malika S. ; Chen, Yannan ; Chauhan, Shradha ; Zhang, Jing ; De La Cruz, Estanislao Daniel ; Gong, Cheng ; Tomer, Raju</creatorcontrib><description>Ketamine is a multifunctional drug with clinical applications as an anesthetic, pain management medication, and a fast-acting antidepressant. However, it is also recreationally abused for its dissociative effects. Recent studies in rodents are revealing the neuronal mechanisms mediating its actions, but the impact of prolonged exposure to ketamine on brain-wide networks remains less understood. Here, we develop a sub-cellular resolution whole-brain phenotyping approach and utilize it in male mice to show that repeated ketamine administration leads to a dose-dependent decrease in dopamine neurons in midbrain regions linked to behavioral states, alongside an increase in the hypothalamus. Additionally, diverse changes are observed in long-range innervations of the prefrontal cortex, striatum, and sensory areas. Furthermore, the data support a role for post-transcriptional regulation in enabling ketamine-induced neural plasticity. Through an unbiased, high-resolution whole-brain analysis, this study provides important insights into how chronic ketamine exposure reshapes brain-wide networks.
[Display omitted]
•Whole-brain mapping of chronic ketamine-induced sub-cellular plasticity in dopamine system•Dose-dependent divergent changes in midbrain and hypothalamic dopamine domains•Divergently altered innervation of prefrontal, striatum, and sensory cortices•Data supporting post-transcriptional regulation of ketamine-induced structural plasticity
Datta et al. develop and use a whole-brain approach to reveal the impact of repeated ketamine exposure on the dopamine system. Findings also support post-transcriptional regulation of ketamine-induced neural network plasticity. This study provides crucial insights into how pharmacological agents like ketamine can reshape brain-wide networks in a non-uniform manner.</description><identifier>ISSN: 2211-1247</identifier><identifier>EISSN: 2211-1247</identifier><identifier>DOI: 10.1016/j.celrep.2023.113491</identifier><identifier>PMID: 38052211</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; antidepressant ; Antidepressive Agents - pharmacology ; Brain ; Brain Mapping ; dopamine ; Dopamine - pharmacology ; ketamine ; Ketamine - pharmacology ; Male ; Mice ; modulation ; neural circuit adaptations ; plasticity ; whole-brain mapping</subject><ispartof>Cell reports (Cambridge), 2023-12, Vol.42 (12), p.113491-113491, Article 113491</ispartof><rights>2023 The Authors</rights><rights>Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-d97a7a7c8e7c98d9c159cca4f77cb07264d426f2082ed5e90f81c26432f3560c3</citedby><cites>FETCH-LOGICAL-c464t-d97a7a7c8e7c98d9c159cca4f77cb07264d426f2082ed5e90f81c26432f3560c3</cites><orcidid>0000-0002-4229-2860</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,783,787,888,27936,27937</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38052211$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Datta, Malika S.</creatorcontrib><creatorcontrib>Chen, Yannan</creatorcontrib><creatorcontrib>Chauhan, Shradha</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>De La Cruz, Estanislao Daniel</creatorcontrib><creatorcontrib>Gong, Cheng</creatorcontrib><creatorcontrib>Tomer, Raju</creatorcontrib><title>Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system</title><title>Cell reports (Cambridge)</title><addtitle>Cell Rep</addtitle><description>Ketamine is a multifunctional drug with clinical applications as an anesthetic, pain management medication, and a fast-acting antidepressant. However, it is also recreationally abused for its dissociative effects. Recent studies in rodents are revealing the neuronal mechanisms mediating its actions, but the impact of prolonged exposure to ketamine on brain-wide networks remains less understood. Here, we develop a sub-cellular resolution whole-brain phenotyping approach and utilize it in male mice to show that repeated ketamine administration leads to a dose-dependent decrease in dopamine neurons in midbrain regions linked to behavioral states, alongside an increase in the hypothalamus. Additionally, diverse changes are observed in long-range innervations of the prefrontal cortex, striatum, and sensory areas. Furthermore, the data support a role for post-transcriptional regulation in enabling ketamine-induced neural plasticity. Through an unbiased, high-resolution whole-brain analysis, this study provides important insights into how chronic ketamine exposure reshapes brain-wide networks.
[Display omitted]
•Whole-brain mapping of chronic ketamine-induced sub-cellular plasticity in dopamine system•Dose-dependent divergent changes in midbrain and hypothalamic dopamine domains•Divergently altered innervation of prefrontal, striatum, and sensory cortices•Data supporting post-transcriptional regulation of ketamine-induced structural plasticity
Datta et al. develop and use a whole-brain approach to reveal the impact of repeated ketamine exposure on the dopamine system. Findings also support post-transcriptional regulation of ketamine-induced neural network plasticity. This study provides crucial insights into how pharmacological agents like ketamine can reshape brain-wide networks in a non-uniform manner.</description><subject>Animals</subject><subject>antidepressant</subject><subject>Antidepressive Agents - pharmacology</subject><subject>Brain</subject><subject>Brain Mapping</subject><subject>dopamine</subject><subject>Dopamine - pharmacology</subject><subject>ketamine</subject><subject>Ketamine - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>modulation</subject><subject>neural circuit adaptations</subject><subject>plasticity</subject><subject>whole-brain mapping</subject><issn>2211-1247</issn><issn>2211-1247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9UctOwzAQtBCIVqV_gFCOXFJsx0nsCwhVvKRKHABxtFxn07okcbDTSv17XKVU5YL3YHt3Zna1g9AlwROCSXazmmioHLQTimkyISRhgpygIaWExISy_PToPUBj71c4nAwTItg5GiQcp7v6EL19Lm0F8dwp00S1alvTLCIHG1CVj7olRIXZgFtA00WmbpXuIltGX9Cp2jQQ2abH2Lb_-63voL5AZ2Wgw3h_j9DH48P79DmevT69TO9nsWYZ6-JC5CqE5pBrwQuhSSq0VqzMcz3HOc1YwWhWUswpFCkIXHKiQzahZZJmWCcjdNfrtut5DYUOQzpVydaZWrmttMrIv5XGLOXCbiTBnCUpp0Hheq_g7PcafCdr48NmK9WAXXtJueAiZZjgAGU9VDvrvYPy0IdgufNErmTvidx5IntPAu3qeMYD6deBALjtARA2tTHgpNcGGg2FcaA7WVjzf4cfX1-f7A</recordid><startdate>20231226</startdate><enddate>20231226</enddate><creator>Datta, Malika S.</creator><creator>Chen, Yannan</creator><creator>Chauhan, Shradha</creator><creator>Zhang, Jing</creator><creator>De La Cruz, Estanislao Daniel</creator><creator>Gong, Cheng</creator><creator>Tomer, Raju</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4229-2860</orcidid></search><sort><creationdate>20231226</creationdate><title>Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system</title><author>Datta, Malika S. ; Chen, Yannan ; Chauhan, Shradha ; Zhang, Jing ; De La Cruz, Estanislao Daniel ; Gong, Cheng ; Tomer, Raju</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-d97a7a7c8e7c98d9c159cca4f77cb07264d426f2082ed5e90f81c26432f3560c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>antidepressant</topic><topic>Antidepressive Agents - pharmacology</topic><topic>Brain</topic><topic>Brain Mapping</topic><topic>dopamine</topic><topic>Dopamine - pharmacology</topic><topic>ketamine</topic><topic>Ketamine - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>modulation</topic><topic>neural circuit adaptations</topic><topic>plasticity</topic><topic>whole-brain mapping</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Datta, Malika S.</creatorcontrib><creatorcontrib>Chen, Yannan</creatorcontrib><creatorcontrib>Chauhan, Shradha</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>De La Cruz, Estanislao Daniel</creatorcontrib><creatorcontrib>Gong, Cheng</creatorcontrib><creatorcontrib>Tomer, Raju</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell reports (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Datta, Malika S.</au><au>Chen, Yannan</au><au>Chauhan, Shradha</au><au>Zhang, Jing</au><au>De La Cruz, Estanislao Daniel</au><au>Gong, Cheng</au><au>Tomer, Raju</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system</atitle><jtitle>Cell reports (Cambridge)</jtitle><addtitle>Cell Rep</addtitle><date>2023-12-26</date><risdate>2023</risdate><volume>42</volume><issue>12</issue><spage>113491</spage><epage>113491</epage><pages>113491-113491</pages><artnum>113491</artnum><issn>2211-1247</issn><eissn>2211-1247</eissn><abstract>Ketamine is a multifunctional drug with clinical applications as an anesthetic, pain management medication, and a fast-acting antidepressant. However, it is also recreationally abused for its dissociative effects. Recent studies in rodents are revealing the neuronal mechanisms mediating its actions, but the impact of prolonged exposure to ketamine on brain-wide networks remains less understood. Here, we develop a sub-cellular resolution whole-brain phenotyping approach and utilize it in male mice to show that repeated ketamine administration leads to a dose-dependent decrease in dopamine neurons in midbrain regions linked to behavioral states, alongside an increase in the hypothalamus. Additionally, diverse changes are observed in long-range innervations of the prefrontal cortex, striatum, and sensory areas. Furthermore, the data support a role for post-transcriptional regulation in enabling ketamine-induced neural plasticity. Through an unbiased, high-resolution whole-brain analysis, this study provides important insights into how chronic ketamine exposure reshapes brain-wide networks.
[Display omitted]
•Whole-brain mapping of chronic ketamine-induced sub-cellular plasticity in dopamine system•Dose-dependent divergent changes in midbrain and hypothalamic dopamine domains•Divergently altered innervation of prefrontal, striatum, and sensory cortices•Data supporting post-transcriptional regulation of ketamine-induced structural plasticity
Datta et al. develop and use a whole-brain approach to reveal the impact of repeated ketamine exposure on the dopamine system. Findings also support post-transcriptional regulation of ketamine-induced neural network plasticity. This study provides crucial insights into how pharmacological agents like ketamine can reshape brain-wide networks in a non-uniform manner.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38052211</pmid><doi>10.1016/j.celrep.2023.113491</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-4229-2860</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cell reports (Cambridge), 2023-12, Vol.42 (12), p.113491-113491, Article 113491 |
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| language | eng |
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| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS |
| subjects | Animals antidepressant Antidepressive Agents - pharmacology Brain Brain Mapping dopamine Dopamine - pharmacology ketamine Ketamine - pharmacology Male Mice modulation neural circuit adaptations plasticity whole-brain mapping |
| title | Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system |
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