Activation of RMTg projections to the VTA reverse cocaine induced molecular adaptation in the reward system

Activation of RMTg projections to the VTA reverse cocaine induced molecular adaptation in the reward system | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Activation of RMTg projections to the VTA reverse cocaine induced molecular adaptation in the reward system Rami Yaka, Alaa Khayat This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3175395/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Jan, 2024 Read the published version in Translational Psychiatry → Version 1 posted 9 You are reading this latest preprint version Abstract The rostromedial tegmental nucleus (RMTg) plays a crucial role in regulating reward-related behavior by exerting inhibitory control over the ventral tegmental area (VTA). This modulation of dopamine neurons activity within the VTA is essential for maintaining homeostasis in the reward system. Recently we have shown that activation of RMTg projections to the VTA during the acquisition of cocaine-conditioned place preference (CPP) reduces the rewarding properties of cocaine and decreases VTA dopamine neuron activity. By inhibiting dopamine neurons in the VTA, we hypothesized that RMTg projections hold the potential to restore reward system homeostasis disrupted by repeated cocaine use, and attenuate molecular adaptations in the reward system, including alterations in signaling pathways. Our study demonstrates that enhancing the GABAergic inputs from the RMTg to the VTA can mitigate cocaine-induced molecular changes in key regions, namely the VTA, nucleus accumbens (NAc), and prefrontal cortex (PFC). Specifically, we found that cocaine-induced alteration in the phosphorylation state of ERK (pERK) and GluA1 on serine 845 (S845) and serine 831 (S831), that play a major role in plasticity by controlling the activity and trafficking of AMPA receptors, were significantly reversed following optic stimulation of RMTg afferents to the VTA. These findings highlight the therapeutic potential of targeting the RMTg-VTA circuitry for mitigating cocaine reward and addiction. Ultimately, this research may pave the way for novel therapeutic interventions that restore balance in the reward system and alleviate the detrimental effects of cocaine. Health sciences/Diseases/Psychiatric disorders/Addiction Biological sciences/Neuroscience/Molecular neuroscience Cocaine GABA VTA RMTg NAc PFC Optogenetics GluA1 ERK Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Additional Declarations The authors have declared there is NO conflict of interest to disclose Cite Share Download PDF Status: Published Journal Publication published 19 Jan, 2024 Read the published version in Translational Psychiatry → Version 1 posted Editorial decision: revise 23 Oct, 2023 Review # 1 received at journal 09 Oct, 2023 Review # 2 received at journal 08 Oct, 2023 Reviewer # 2 agreed at journal 25 Sep, 2023 Reviewer # 1 agreed at journal 25 Sep, 2023 Reviewers invited by journal 25 Sep, 2023 Submission checks completed at journal 17 Jul, 2023 Editor assigned by journal 16 Jul, 2023 First submitted to journal 16 Jul, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3175395","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":235860352,"identity":"34191a09-9a2b-4727-9180-a06f2c350c3e","order_by":0,"name":"Rami Yaka","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYFACNgaGDwzMDAYMDAkHwHx2IrQwzkDRwkyEFmYeiBYoIKTF4PixxM+2OdYM5hIJDw8w1Ngx8BHUcibtsHTutnQGyxkJQIcdSybsMIMD6Q1ALYcZDG6AtLAdIELL+efNvy3hWv4Ro+VG2jFpRpgWxjYitEjeeJZm2bstncfgzIOEA4l9yTwEtfCdTzO+8XObtZzB8ZzkDx++2cnJtzfg16JwAELzAFECQwKYQQDII4xkP0BQ9SgYBaNgFIxMAACyb0Fcyk6CtAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-2372-2957","institution":"Hebrew University of Jerusalem","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Rami","middleName":"","lastName":"Yaka","suffix":""},{"id":235860353,"identity":"b299842d-a252-4f63-9155-2e76306cbec6","order_by":1,"name":"Alaa Khayat","email":"","orcid":"","institution":"Hebrew University of Jerusalem","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alaa","middleName":"","lastName":"Khayat","suffix":""}],"badges":[],"createdAt":"2023-07-16 15:20:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3175395/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3175395/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41398-024-02763-9","type":"published","date":"2024-01-19T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":44042287,"identity":"8d8196f9-920c-4350-8d96-3300c36817b4","added_by":"auto","created_at":"2023-10-03 20:49:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":234399,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"11.png","url":"https://assets-eu.researchsquare.com/files/rs-3175395/v1/1eec029ad41d7a1f7a59dd62.png"},{"id":44042288,"identity":"0364b607-8ec9-47ca-b209-9f3c0e3ebf73","added_by":"auto","created_at":"2023-10-03 20:49:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":170129,"visible":true,"origin":"","legend":"\u003cp\u003eEnhanced GABAergic tone from the RMTg during conditioning to cocaine attenuates changes in ERK, PERK and GluA1ps845 in the VTA.\u003c/p\u003e\n\u003cp\u003eAll rats were euthanized 45 minutes after the RePP test. Then, their VTA was taken out and homogenized. Samples were resolved by SDS-PAGE, and WB membranes were probed with the appropriate antibodies. A. The bar histograms depict the level of ERK divided by Actin, rats treated with cocaine (15 mg/kg) displayed significantly lower values compared to all other groups (P \u0026lt; 0.001), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,29) = 9.199, P \u0026lt; 0.01, FGROUP(1,29) = 10.13, P \u0026lt; 0.01, FINTERACTION (1,29) = 9.441, P \u0026lt; 0.01, followed by Tukey’s multiple comparison test]. (n = 8, 7, 9, and 9 for saline -, saline +, cocaine-, and cocaine+ groups, respectively). B. The bar histograms depict the level of pERK (Thr202/Tyr204) divided by ERK antibodies, rats treated with cocaine (15 mg/kg) displayed significantly higher values compared to all other groups (P \u0026lt; 0.001), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,16) = 5.075, P \u0026lt; 0.05, FGROUP(1,16) = 12.3, P \u0026lt; 0.01, FINTERACTION (1,16) = 22.18, P \u0026lt; 0.001, followed by Tukey’s multiple comparison test]. (n = 5 for all groups). C. The bar histograms depict the level of GluA1 divided by Actin. No significant difference was found [FOPTIC STIMULATION (1,18) = 1.112, P \u0026gt; 0.05, FGROUP(1,18) = 3.486, P \u0026gt; 0.05, FINTERACTION (1,18) = 2.292, P \u0026gt; 0.05, two-way ANOVA followed by Tukey’s multiple comparison test]. (n = 5 for the saline groups, n = 6 for the cocaine groups). D. The bar histograms depict the level of GluA1ps845 divided by GluA1 antibodies, rats treated with cocaine (15 mg/kg) displayed significantly higher values compared to saline-treated rats (P \u0026lt; 0.05), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,17) = 0.5023, P \u0026gt; 0.05, FGROUP(1,17) = 2.699, P \u0026gt; 0.05, FINTERACTION (1,17) = 7.414, P \u0026lt; 0.05, followed by Tukey’s multiple comparison test]. (n = 4, 5, 6, and 6 for saline -, saline +, cocaine-, and cocaine+ groups, respectively). E. The bar histograms depict the level of GluA1ps831 divided by GluA1 antibodies, rats treated with cocaine (15 mg/kg) with optic stimulation displayed significantly lower values compared to the saline with optic stimulation and saline without optic stimulation groups (P \u0026lt; 0.05), as determined by a two-way ANOVA test. A nonsignificant reduction was found in the cocaine-treated group compared to the saline with optic stimulation and saline without optic stimulation groups [FOPTIC STIMULATION (1,14) = 0.3760, P \u0026gt; 0.05, FGROUP(1,14) = 14.33, P \u0026lt; 0.01, FINTERACTION (1,14) = 0.9373, P \u0026gt; 0.05, followed by Tukey’s multiple comparison test]. (n = 4 for the saline groups, n = 5 for the cocaine groups). (- O.S refers to - optic stimulation, whereas + O.S refers to + optic stimulation).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3175395/v1/7525e500f7dc3ce7fac48cf8.png"},{"id":44042289,"identity":"96e3cd63-85f3-4ca7-904b-e97408b0b1f9","added_by":"auto","created_at":"2023-10-03 20:49:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":135740,"visible":true,"origin":"","legend":"\u003cp\u003eEnhanced GABAergic tone from the RMTg during conditioning to cocaine attenuates changes in PERK, GluA1ps845 and GluA1ps831 in the NAc.\u003c/p\u003e\n\u003cp\u003eAll rats were euthanized 45 minutes after the RePP test. Then, their NAc was taken out and homogenized. Samples were resolved by SDS-PAGE, and WB membranes were probed with the appropriate antibodies. A. The bar histograms depict the level of ERK divided by Actin, no significant difference was found (P \u0026gt; 0.05), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,8) = 1.456, P \u0026gt; 0.05, FGROUP (1,8) = 2.635, P \u0026gt; 0.05, FINTERACTION (1,8) = 5.095, P \u0026gt; 0.05, followed by Tukey’s multiple comparison test]. (n = 3 for all groups). B. The bar histograms depict the level of pERK (Thr202/Tyr204) divided by ERK antibodies, rats treated with cocaine (15 mg/kg) displayed significantly higher values compared to all other groups (P \u0026lt; 0.05), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,20) = 4.809, P \u0026lt; 0.05, FGROUP (1,20) = 6.547, P \u0026lt; 0.05, FINTERACTION (1,20) = 4.335, P = 0.0504, followed by Tukey’s multiple comparison test]. (n = 5, 6, 7, and 6 for saline -, saline +, cocaine-, and cocaine+ groups, respectively). C. The bar histograms depict the level of GluA1 divided by Actin, no significant difference was found [FOPTIC STIMULATION (1,10) = 3.39, P \u0026gt; 0.05, FGROUP (1,10) = 1.603, P \u0026gt; 0.05, FINTERACTION (1,10) = 1.605, P \u0026gt; 0.05, two-way ANOVA followed by Tukey’s multiple comparison test]. (n = 3 for saline groups, n = 4 for cocaine groups). D. The bar histograms depict the level of GluA1ps845 divided by GluA1 antibodies, rats treated with cocaine (15 mg/kg) displayed significantly higher values compared to all other groups (P \u0026lt; 0.05), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,9) = 4.275, P \u0026gt; 0.05, FGROUP (1,9) = 13.35, P \u0026lt; 0.01, FINTERACTION (1,9) = 6.738, P \u0026lt; 0.05, followed by Tukey’s multiple comparison test]. (n = 3, 3, 4, and 3 for saline -, saline +, cocaine-, and cocaine+ groups, respectively). E. The bar histograms depict the level of GluA1ps831 divided by GluA1 antibodies, rats treated with cocaine (15 mg/kg) without optic stimulation displayed significantly higher values compared to all other groups (P \u0026lt; 0.05), as determined by a two-way ANOVA test. [FOPTIC STIMULATION (1,10) = 6.500, P \u0026lt; 0.05, FGROUP (1,10) = 5.396, P \u0026lt; 0.05, FINTERACTION (1,10) = 4.019, P \u0026gt; 0.05, followed by Tukey’s multiple comparison test]. (n = 3 for the saline groups, n = 4 for the cocaine groups). (- O.S refers to - optic stimulation, whereas + O.S refers to + optic stimulation).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3175395/v1/ac1dc4d3ab2044744e770089.png"},{"id":44042290,"identity":"4d0f4a97-9818-4326-8ef6-fdf342fa76aa","added_by":"auto","created_at":"2023-10-03 20:49:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":140172,"visible":true,"origin":"","legend":"\u003cp\u003eEnhanced GABAergic tone from the RMTg during conditioning to cocaine attenuates changes in GluA1ps831 but not GluA1ps845 in the PFC.\u003c/p\u003e\n\u003cp\u003eAll rats were euthanized 45 minutes after the RePP test. Then, their PFC were taken out and homogenized. Samples were resolved by SDS-PAGE, and WB membranes were probed with the appropriate antibodies. A. The bar histograms depict the level of ERK divided by Actin, no significant difference was found (P \u0026gt; 0.05), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,10) = 0.003651, P \u0026gt; 0.05, FGROUP (1,10) = 2.211, P \u0026gt; 0.05, FINTERACTION (1,10) = 0.2461, P \u0026gt; 0.05, followed by Tukey’s multiple comparison test]. (n = 3 for the saline groups, n = 4 for the cocaine groups). B. The bar histograms depict the level of pERK (Thr202/Tyr204) divided by ERK antibodies, no significant difference was found (P \u0026gt; 0.05), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,10) = 0.01467, P \u0026gt; 0.05, FGROUP (1,10) = 4.050, P \u0026gt; 0.05, FINTERACTION (1,10) = 1.125, P \u0026gt; 0.05, followed by Tukey’s multiple comparison test]. (n = 3 for the saline groups, n = 4 for the cocaine groups). C. The bar histograms depict the level of GluA1 divided by Actin, no significant difference was found (P \u0026gt; 0.05), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,10) = 0.04842, P \u0026gt; 0.05, FGROUP (1,10) = 0.7459, P \u0026gt; 0.05, FINTERACTION (1,10) = 0.03048, P \u0026gt; 0.05, followed by Tukey’s multiple comparison test]. (n = 3 for the saline groups, n = 4 for the cocaine groups). D. The bar histograms depict the level of GluA1ps845 divided by GluA1 antibodies, rats treated with cocaine (15 mg/kg) displayed significantly higher values compared to the saline without optic stimulation and saline with optic stimulation groups (P \u0026lt; 0.05), no significant difference was found between the cocaine group and cocaine with optic stimulation group (P \u0026gt; 0.05), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,18) = 0.003881, P \u0026gt; 0.05, FGROUP (1,18) = 16.48, P \u0026lt; 0.001, FINTERACTION (1,18) = 0.0005230, P \u0026gt; 0.05, followed by Tukey’s multiple comparison test]. (n = 5 for the saline groups, n = 6 for the cocaine groups). E. The bar histograms depict the level of GluA1ps831 divided by GluA1 antibodies, rats treated with cocaine (15 mg/kg) displayed significantly higher values compared to all other groups (P \u0026lt; 0.05 for saline- optic stimulation, P \u0026lt; 0.001 for saline + optic stimulation and cocaine+ optic stimulation groups), as determined by a two-way ANOVA test [FOPTIC STIMULATION (1,19) = 24.75, P \u0026lt; 0.0001, FGROUP (1,19) = 3.460, P \u0026gt; 0.05, FINTERACTION (1,19) = 10.23, P \u0026lt; 0.01, followed by Tukey’s multiple comparison test]. (n = 6 for the saline groups, n = 5, and 6 for the cocaine - and cocaine + groups, respectively). (- O.S refers to - optic stimulation, whereas + O.S refers to + optic stimulation).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3175395/v1/6aaa0ac785cf864e1080665e.png"},{"id":49925142,"identity":"e1ea6c4c-b261-491e-820b-4175143d7fd3","added_by":"auto","created_at":"2024-01-21 08:07:28","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":831979,"visible":true,"origin":"","legend":"","description":"","filename":"Khayatetal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3175395/v1_covered_ee75b667-d675-49a0-ac7f-7ce46bf8bac2.pdf"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose","formattedTitle":"Activation of RMTg projections to the VTA reverse cocaine induced molecular adaptation in the reward system","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"translational-psychiatry","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tp","sideBox":"Learn more about [Translational Psychiatry](http://www.nature.com/tp/)","snPcode":"41398","submissionUrl":"https://mts-tp.nature.com/cgi-bin/main.plex","title":"Translational Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cocaine, GABA, VTA, RMTg, NAc, PFC, Optogenetics, GluA1, ERK","lastPublishedDoi":"10.21203/rs.3.rs-3175395/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3175395/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The rostromedial tegmental nucleus (RMTg) plays a crucial role in regulating reward-related behavior by exerting inhibitory control over the ventral tegmental area (VTA). This modulation of dopamine neurons activity within the VTA is essential for maintaining homeostasis in the reward system. Recently we have shown that activation of RMTg projections to the VTA during the acquisition of cocaine-conditioned place preference (CPP) reduces the rewarding properties of cocaine and decreases VTA dopamine neuron activity. By inhibiting dopamine neurons in the VTA, we hypothesized that RMTg projections hold the potential to restore reward system homeostasis disrupted by repeated cocaine use, and attenuate molecular adaptations in the reward system, including alterations in signaling pathways. Our study demonstrates that enhancing the GABAergic inputs from the RMTg to the VTA can mitigate cocaine-induced molecular changes in key regions, namely the VTA, nucleus accumbens (NAc), and prefrontal cortex (PFC). Specifically, we found that cocaine-induced alteration in the phosphorylation state of ERK (pERK) and GluA1 on serine 845 (S845) and serine 831 (S831), that play a major role in plasticity by controlling the activity and trafficking of AMPA receptors, were significantly reversed following optic stimulation of RMTg afferents to the VTA. These findings highlight the therapeutic potential of targeting the RMTg-VTA circuitry for mitigating cocaine reward and addiction. Ultimately, this research may pave the way for novel therapeutic interventions that restore balance in the reward system and alleviate the detrimental effects of cocaine.","manuscriptTitle":"Activation of RMTg projections to the VTA reverse cocaine induced molecular adaptation in the reward system","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-03 20:49:19","doi":"10.21203/rs.3.rs-3175395/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2023-10-23T13:19:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2023-10-09T21:36:59+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2023-10-08T12:47:20+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2023-09-25T15:14:28+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2023-09-25T15:09:24+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2023-09-25T12:43:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-07-17T10:06:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-07-16T15:15:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Translational Psychiatry","date":"2023-07-16T15:15:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"translational-psychiatry","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tp","sideBox":"Learn more about [Translational Psychiatry](http://www.nature.com/tp/)","snPcode":"41398","submissionUrl":"https://mts-tp.nature.com/cgi-bin/main.plex","title":"Translational Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"32984773-e8b8-422f-af20-25935bd53fe8","owner":[],"postedDate":"October 3rd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":24979065,"name":"Health sciences/Diseases/Psychiatric disorders/Addiction"},{"id":24979066,"name":"Biological sciences/Neuroscience/Molecular neuroscience"}],"tags":[],"updatedAt":"2024-01-21T08:07:15+00:00","versionOfRecord":{"articleIdentity":"rs-3175395","link":"https://doi.org/10.1038/s41398-024-02763-9","journal":{"identity":"translational-psychiatry","isVorOnly":false,"title":"Translational Psychiatry"},"publishedOn":"2024-01-19 05:00:00","publishedOnDateReadable":"January 19th, 2024"},"versionCreatedAt":"2023-10-03 20:49:19","video":"","vorDoi":"10.1038/s41398-024-02763-9","vorDoiUrl":"https://doi.org/10.1038/s41398-024-02763-9","workflowStages":[]},"version":"v1","identity":"rs-3175395","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3175395","identity":"rs-3175395","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}