A translational perspective on the anti-anhedonic effect of ketamine and its neural underpinnings
Anhedonia, a pronounced reduction in interest or pleasure in any of life’s daily activities, is a cardinal symptom of major depression. In this Perspective article, we synthesise the recent evidence from rodent, monkey and human neuroimaging literature to highlight how the habenula, a small evolutio...
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| Veröffentlicht in: | Molecular psychiatry 2022-01, Vol.27 (1), p.81-87 |
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| creator | Pulcu, Erdem Guinea, Calum Cowen, Philip J. Murphy, Susannah E. Harmer, Catherine J. |
| description | Anhedonia, a pronounced reduction in interest or pleasure in any of life’s daily activities, is a cardinal symptom of major depression. In this
Perspective
article, we synthesise the recent evidence from rodent, monkey and human neuroimaging literature to highlight how the habenula, a small evolutionarily conserved subcortical structure located in the midbrain, may orchestrate the behavioural expression of anhedonia across fronto-mesolimbic networks. We then review how this circuitry can be modulated by ketamine, an NMDA receptor antagonist with rapid antidepressant properties. We propose that experimental paradigms founded in reinforcement learning and value-based decision-making can usefully probe this network and thereby help elucidate the mechanisms underlying ketamine’s rapid antidepressant action. |
| doi_str_mv | 10.1038/s41380-021-01183-1 |
| format | Article |
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Perspective
article, we synthesise the recent evidence from rodent, monkey and human neuroimaging literature to highlight how the habenula, a small evolutionarily conserved subcortical structure located in the midbrain, may orchestrate the behavioural expression of anhedonia across fronto-mesolimbic networks. We then review how this circuitry can be modulated by ketamine, an NMDA receptor antagonist with rapid antidepressant properties. We propose that experimental paradigms founded in reinforcement learning and value-based decision-making can usefully probe this network and thereby help elucidate the mechanisms underlying ketamine’s rapid antidepressant action.</description><identifier>ISSN: 1359-4184</identifier><identifier>ISSN: 1476-5578</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/s41380-021-01183-1</identifier><identifier>PMID: 34158619</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>59/36 ; 59/57 ; 59/78 ; 631/378 ; 631/477 ; 64/60 ; Anhedonia ; Antidepressive Agents - pharmacology ; Antidepressive Agents - therapeutic use ; Behavior ; Behavioral Sciences ; Biological Psychology ; Decision making ; Depressive Disorder, Major - drug therapy ; Dopamine ; Glutamic acid receptors (ionotropic) ; Habenula ; Hedonic response ; Humans ; Ketamine ; Ketamine - pharmacology ; Ketamine - therapeutic use ; Medical imaging ; Medicine ; Medicine & Public Health ; Mental depression ; Mesencephalon ; Mesolimbic system ; N-Methyl-D-aspartic acid receptors ; Neuroimaging ; Neurosciences ; Perspective ; Pharmacotherapy ; Psychiatry ; Receptors, N-Methyl-D-Aspartate - metabolism</subject><ispartof>Molecular psychiatry, 2022-01, Vol.27 (1), p.81-87</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-c2298b3adbdec1ebb4fc1c57913682ed17b4a021022e55d993ceebece6d8d6b23</citedby><cites>FETCH-LOGICAL-c474t-c2298b3adbdec1ebb4fc1c57913682ed17b4a021022e55d993ceebece6d8d6b23</cites><orcidid>0000-0002-1609-8335 ; 0000-0001-5518-6138 ; 0000-0001-8995-2099</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34158619$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pulcu, Erdem</creatorcontrib><creatorcontrib>Guinea, Calum</creatorcontrib><creatorcontrib>Cowen, Philip J.</creatorcontrib><creatorcontrib>Murphy, Susannah E.</creatorcontrib><creatorcontrib>Harmer, Catherine J.</creatorcontrib><title>A translational perspective on the anti-anhedonic effect of ketamine and its neural underpinnings</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>Anhedonia, a pronounced reduction in interest or pleasure in any of life’s daily activities, is a cardinal symptom of major depression. In this
Perspective
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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pulcu, Erdem</au><au>Guinea, Calum</au><au>Cowen, Philip J.</au><au>Murphy, Susannah E.</au><au>Harmer, Catherine J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A translational perspective on the anti-anhedonic effect of ketamine and its neural underpinnings</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2022-01-01</date><risdate>2022</risdate><volume>27</volume><issue>1</issue><spage>81</spage><epage>87</epage><pages>81-87</pages><issn>1359-4184</issn><issn>1476-5578</issn><eissn>1476-5578</eissn><abstract>Anhedonia, a pronounced reduction in interest or pleasure in any of life’s daily activities, is a cardinal symptom of major depression. In this
Perspective
article, we synthesise the recent evidence from rodent, monkey and human neuroimaging literature to highlight how the habenula, a small evolutionarily conserved subcortical structure located in the midbrain, may orchestrate the behavioural expression of anhedonia across fronto-mesolimbic networks. We then review how this circuitry can be modulated by ketamine, an NMDA receptor antagonist with rapid antidepressant properties. We propose that experimental paradigms founded in reinforcement learning and value-based decision-making can usefully probe this network and thereby help elucidate the mechanisms underlying ketamine’s rapid antidepressant action.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34158619</pmid><doi>10.1038/s41380-021-01183-1</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-1609-8335</orcidid><orcidid>https://orcid.org/0000-0001-5518-6138</orcidid><orcidid>https://orcid.org/0000-0001-8995-2099</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 59/36 59/57 59/78 631/378 631/477 64/60 Anhedonia Antidepressive Agents - pharmacology Antidepressive Agents - therapeutic use Behavior Behavioral Sciences Biological Psychology Decision making Depressive Disorder, Major - drug therapy Dopamine Glutamic acid receptors (ionotropic) Habenula Hedonic response Humans Ketamine Ketamine - pharmacology Ketamine - therapeutic use Medical imaging Medicine Medicine & Public Health Mental depression Mesencephalon Mesolimbic system N-Methyl-D-aspartic acid receptors Neuroimaging Neurosciences Perspective Pharmacotherapy Psychiatry Receptors, N-Methyl-D-Aspartate - metabolism |
| title | A translational perspective on the anti-anhedonic effect of ketamine and its neural underpinnings |
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