{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:04:41Z","timestamp":1792065881138,"version":"4.4.0"},"reference-count":87,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurochem Res"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1007\/s11064-025-04655-w","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T10:29:49Z","timestamp":1767781789000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deep Brain Stimulation of Lateral Habenula Ameliorates Depression-like Symptoms in Rats: Involvement of Mesolimbic Circuit"],"prefix":"10.1007","volume":"51","author":[{"given":"Hemant S.","family":"Kanhere","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dadasaheb M.","family":"Kokare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh R.","family":"Jogdand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biru B.","family":"Dudhabhate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishikant K.","family":"Subhedar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"4655_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21239234","volume":"21","author":"OV Averina","year":"2020","unstructured":"Averina OV, Zorkina YA, Yunes RA et al (2020) Bacterial metabolites of human gut microbiota correlating with depression. Int J Mol Sci 21:1\u201340. https:\/\/doi.org\/10.3390\/ijms21239234","journal-title":"Int J Mol Sci"},{"key":"4655_CR2","doi-asserted-by":"publisher","first-page":"369","DOI":"10.2147\/PPA.S29716","volume":"6","author":"KS Al-Harbi","year":"2012","unstructured":"Al-Harbi KS (2012) Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence 6:369\u2013388","journal-title":"Patient Prefer Adherence"},{"key":"4655_CR3","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.neuron.2005.02.014","volume":"45","author":"HS Mayberg","year":"2005","unstructured":"Mayberg HS, Lozano AM, Voon V et al (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45:651\u2013660. https:\/\/doi.org\/10.1016\/j.neuron.2005.02.014","journal-title":"Neuron"},{"key":"4655_CR4","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1016\/j.neubiorev.2012.06.001","volume":"36","author":"RJ Anderson","year":"2012","unstructured":"Anderson RJ, Frye MA, Abulseoud OA et al (2012) Deep brain stimulation for treatment-resistant depression: Efficacy, safety and mechanisms of action. Neurosci Biobehav Rev 36:1920\u20131933","journal-title":"Neurosci Biobehav Rev"},{"key":"4655_CR5","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1038\/mp.2018.2","volume":"23","author":"MP Dandekar","year":"2018","unstructured":"Dandekar MP, Fenoy AJ, Carvalho AF et al (2018) Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications. Mol Psychiatry 23:1094\u20131112. https:\/\/doi.org\/10.1038\/mp.2018.2","journal-title":"Mol Psychiatry"},{"key":"4655_CR6","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.pnpbp.2017.11.012","volume":"82","author":"C Zhou","year":"2018","unstructured":"Zhou C, Zhang H, Qin Y et al (2018) A systematic review and meta-analysis of deep brain stimulation in treatment-resistant depression. Prog Neuropsychopharmacol Biol Psychiatry 82:224\u2013232. https:\/\/doi.org\/10.1016\/j.pnpbp.2017.11.012","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"4655_CR7","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1002\/(SICI)1096-9861(19990428)407:1<130::AID-CNE10>3.0.CO;2-8","volume":"407","author":"KH Andres","year":"1999","unstructured":"Andres KH, Von D\u00fcring M, Veh RW (1999) Subnuclear organization of the rat habenular complexes. J Comp Neurol 407:130\u2013150. https:\/\/doi.org\/10.1002\/(SICI)1096-9861(19990428)407:1%3C130::AID-CNE10%3E3.0.CO;2-8","journal-title":"J Comp Neurol"},{"key":"4655_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/862048","volume":"2014","author":"M Fakhoury","year":"2014","unstructured":"Fakhoury M, Dom\u00ednguez L\u00f3pez S (2014) The role of Habenula in motivation and reward. Adv Neurosci 2014:1\u20136. https:\/\/doi.org\/10.1155\/2014\/862048","journal-title":"Adv Neurosci"},{"key":"4655_CR9","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1038\/nrn3371","volume":"13","author":"ML Concha","year":"2012","unstructured":"Concha ML, Bianco IH, Wilson SW (2012) Encoding asymmetry within neural circuits. Nat Rev Neurosci 13:832\u2013843","journal-title":"Nat Rev Neurosci"},{"key":"4655_CR10","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nrn2866","volume":"11","author":"O Hikosaka","year":"2010","unstructured":"Hikosaka O (2010) The habenula: from stress evasion to value-based decision-making. Nat Rev Neurosci 11:503\u2013513","journal-title":"Nat Rev Neurosci"},{"key":"4655_CR11","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/nn.3779","volume":"17","author":"CD Proulx","year":"2014","unstructured":"Proulx CD, Hikosaka O, Malinow R (2014) Reward processing by the lateral Habenula in normal and depressive behaviors. Nat Neurosci 17:1146\u20131152","journal-title":"Nat Neurosci"},{"key":"4655_CR12","doi-asserted-by":"crossref","unstructured":"Hikosaka O, Sesack SR, Lecourtier L, Shepard PD (2008) Habenula: crossroad between the basal ganglia and the limbic system. In: J Neurosci. pp 11825\u201311829","DOI":"10.1523\/JNEUROSCI.3463-08.2008"},{"key":"4655_CR13","doi-asserted-by":"publisher","first-page":"5485","DOI":"10.1093\/cercor\/bhw316","volume":"27","author":"V Mathis","year":"2017","unstructured":"Mathis V, Barbelivien A, Majchrzak M et al (2017) The lateral Habenula as a relay of cortical information to process working memory. Cereb Cortex 27:5485\u20135495. https:\/\/doi.org\/10.1093\/cercor\/bhw316","journal-title":"Cereb Cortex"},{"key":"4655_CR14","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.tins.2017.06.001","volume":"40","author":"SJY Mizumori","year":"2017","unstructured":"Mizumori SJY, Baker PM (2017) The lateral Habenula and adaptive behaviors. Trends Neurosci 40:481\u2013493","journal-title":"Trends Neurosci"},{"key":"4655_CR15","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.pbb.2017.06.007","volume":"162","author":"B Ba\u00f1o-Ot\u00e1lora","year":"2017","unstructured":"Ba\u00f1o-Ot\u00e1lora B, Piggins HD (2017) Contributions of the lateral Habenula to circadian timekeeping. Pharmacol Biochem Behav 162:46\u201354","journal-title":"Pharmacol Biochem Behav"},{"key":"4655_CR16","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.pbb.2017.06.013","volume":"162","author":"J Mendoza","year":"2017","unstructured":"Mendoza J (2017) Circadian neurons in the lateral habenula: clocking motivated behaviors. Pharmacol Biochem Behav 162:55\u201361","journal-title":"Pharmacol Biochem Behav"},{"key":"4655_CR17","doi-asserted-by":"crossref","unstructured":"Germann J, Mameli M, Elias GJB et al (2021) Deep brain stimulation of the habenula: systematic review of the literature and clinical trial registries. Front Psychiatry 12","DOI":"10.3389\/fpsyt.2021.730931"},{"key":"4655_CR18","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.conb.2017.10.024","volume":"48","author":"Y Yang","year":"2018","unstructured":"Yang Y, Wang H, Hu J, Hu H (2018) Lateral Habenula in the pathophysiology of depression. Curr Opin Neurobiol 48:90\u201396","journal-title":"Curr Opin Neurobiol"},{"key":"4655_CR19","doi-asserted-by":"publisher","unstructured":"Li G, Bo B, Wang P et al (2023) Instantaneous antidepressant effect of lateral Habenula deep brain stimulation in rats studied with functional MRI. https:\/\/doi.org\/10.7554\/eLife.84693. Elife 12:","DOI":"10.7554\/eLife.84693"},{"key":"4655_CR20","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.brainres.2011.08.041","volume":"1422","author":"H Meng","year":"2011","unstructured":"Meng H, Wang Y, Huang M et al (2011) Chronic deep brain stimulation of the lateral Habenula nucleus in a rat model of depression. Brain Res 1422:32\u201338. https:\/\/doi.org\/10.1016\/j.brainres.2011.08.041","journal-title":"Brain Res"},{"key":"4655_CR21","doi-asserted-by":"publisher","unstructured":"Quina LA, Walker A, Morton G et al (2020) GAD2 expression defines a class of excitatory lateral Habenula neurons in mice that project to the Raphe and Pontine tegmentum. https:\/\/doi.org\/10.1523\/ENEURO.0527-19.2020. eNeuro 7:","DOI":"10.1523\/ENEURO.0527-19.2020"},{"key":"4655_CR22","doi-asserted-by":"crossref","unstructured":"Browne CA, Hammack R, Lucki I (2018) Dysregulation of the lateral Habenula in major depressive disorder. Front Synaptic Neurosci 10","DOI":"10.3389\/fnsyn.2018.00046"},{"key":"4655_CR23","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/s41583-020-0292-4","volume":"21","author":"H Hu","year":"2020","unstructured":"Hu H, Cui Y, Yang Y (2020) Circuits and functions of the lateral Habenula in health and in disease. Nat Rev Neurosci 21:277\u2013295","journal-title":"Nat Rev Neurosci"},{"key":"4655_CR24","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1111\/j.1460-9568.2009.06924.x.Lateral","volume":"30","author":"N Omelchenko","year":"2009","unstructured":"Omelchenko N, Bell R, Sesack SR (2009) Lateral Habenula projections to the rat ventral tegmental area: sparse synapses observed onto dopamine and GABA neurons. Eur J Neurosci 30:1239\u20131250. https:\/\/doi.org\/10.1111\/j.1460-9568.2009.06924.x.Lateral","journal-title":"Eur J Neurosci"},{"key":"4655_CR25","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1523\/JNEUROSCI.1353-16.2016","volume":"37","author":"PL Brown","year":"2017","unstructured":"Brown PL, Palacorolla H, Brady D et al (2017) Habenula-induced Inhibition of midbrain dopamine neurons is diminished by lesions of the Rostromedial tegmental nucleus. J Neurosci 37:217\u2013225. https:\/\/doi.org\/10.1523\/JNEUROSCI.1353-16.2016","journal-title":"J Neurosci"},{"key":"4655_CR26","doi-asserted-by":"publisher","unstructured":"Zhang Y, Ma L, Zhang X et al (2023) Deep brain stimulation in the lateral Habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats. Neurobiol Dis 180. https:\/\/doi.org\/10.1016\/j.nbd.2023.106069","DOI":"10.1016\/j.nbd.2023.106069"},{"key":"4655_CR27","doi-asserted-by":"publisher","first-page":"291","DOI":"10.31887\/dcns.2008.10.3\/pgorwood","volume":"10","author":"P Gorwood","year":"2008","unstructured":"Gorwood P (2008) Neurobiological mechanisms of anhedonia. Dialogues Clin Neurosci 10:291\u2013299. https:\/\/doi.org\/10.31887\/dcns.2008.10.3\/pgorwood","journal-title":"Dialogues Clin Neurosci"},{"key":"4655_CR28","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s00213-010-1836-5","volume":"210","author":"SR Ebner","year":"2010","unstructured":"Ebner SR, Roitman MF, Potter DN et al (2010) Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens. Psychopharmacology 210:241\u2013252. https:\/\/doi.org\/10.1007\/s00213-010-1836-5","journal-title":"Psychopharmacology"},{"key":"4655_CR29","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.neuroscience.2024.07.052","volume":"556","author":"BB Dudhabhate","year":"2024","unstructured":"Dudhabhate BB, Awathale SN, Choudhary AG et al (2024) Deep brain stimulation targeted at lateral hypothalamus-medial forebrain bundle reverses depressive-like symptoms and related cognitive deficits in rat: role of serotoninergic system. Neuroscience 556:96\u2013113. https:\/\/doi.org\/10.1016\/j.neuroscience.2024.07.052","journal-title":"Neuroscience"},{"key":"4655_CR30","unstructured":"George Paxinos and Charles Watson (1998) The rat brain in stereotaxic coordinates, Third Edition. Academic Press"},{"key":"4655_CR31","doi-asserted-by":"publisher","unstructured":"Choudhary AG, Awathale SN, Subhedar NK, Kokare DM (2022) In-house fabrication of bipolar electrode-cannula assembly for electrical stimulation and drug delivery at the same site in rat brain. J Pharmacol Toxicol Methods 118. https:\/\/doi.org\/10.1016\/j.vascn.2022.107194","DOI":"10.1016\/j.vascn.2022.107194"},{"key":"4655_CR32","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.vascn.2011.08.002","volume":"64","author":"DM Kokare","year":"2011","unstructured":"Kokare DM, Shelkar GP, Borkar CD et al (2011) A simple and inexpensive method to fabricate a cannula system for intracranial injections in rats and mice. J Pharmacol Toxicol Methods 64:246\u2013250. https:\/\/doi.org\/10.1016\/j.vascn.2011.08.002","journal-title":"J Pharmacol Toxicol Methods"},{"key":"4655_CR33","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.vascn.2013.12.006","volume":"69","author":"SJ Desai","year":"2014","unstructured":"Desai SJ, Bharne AP, Upadhya MA et al (2014) A simple and economical method of electrode fabrication for brain self-stimulation in rats. J Pharmacol Toxicol Methods 69:141\u2013149. https:\/\/doi.org\/10.1016\/j.vascn.2013.12.006","journal-title":"J Pharmacol Toxicol Methods"},{"key":"4655_CR34","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nature09742","volume":"470","author":"B Li","year":"2011","unstructured":"Li B, Piriz J, Mirrione M et al (2011) Synaptic potentiation onto Habenula neurons in the learned helplessness model of depression. Nature 470:535\u2013541. https:\/\/doi.org\/10.1038\/nature09742","journal-title":"Nature"},{"key":"4655_CR35","doi-asserted-by":"publisher","first-page":"4364","DOI":"10.1007\/s12035-018-1381-5","volume":"56","author":"MP Dandekar","year":"2019","unstructured":"Dandekar MP, Saxena A, Scaini G et al (2019) Medial forebrain bundle deep brain stimulation reverses Anhedonic-Like behavior in a chronic model of depression: importance of BDNF and inflammatory cytokines. Mol Neurobiol 56:4364\u20134380. https:\/\/doi.org\/10.1007\/s12035-018-1381-5","journal-title":"Mol Neurobiol"},{"key":"4655_CR36","doi-asserted-by":"publisher","unstructured":"Basu S, Dudhabhate BB, Mitra S et al (2025) Transient receptor potential vanilloid 2 (TRPV2) channels modulate the nigrostriatal dopaminergic activity in rats. Neuropharmacology 278. https:\/\/doi.org\/10.1016\/j.neuropharm.2025.110545","DOI":"10.1016\/j.neuropharm.2025.110545"},{"key":"4655_CR37","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.bbr.2019.01.008","volume":"362","author":"Y Ye","year":"2019","unstructured":"Ye Y, Yao S, Wang R et al (2019) PI3K\/Akt\/NF-\u03baB signaling pathway regulates behaviors in adolescent female rats following with neonatal maternal deprivation and chronic mild stress. Behav Brain Res 362:199\u2013207. https:\/\/doi.org\/10.1016\/j.bbr.2019.01.008","journal-title":"Behav Brain Res"},{"key":"4655_CR38","doi-asserted-by":"publisher","unstructured":"Kawade HM, Patil UP, Pandhare DM et al (2025) Neuropeptide S system mediates nicotine-induced reward-facilitatory behavior. Neuropharmacology 278. https:\/\/doi.org\/10.1016\/j.neuropharm.2025.110543","DOI":"10.1016\/j.neuropharm.2025.110543"},{"key":"4655_CR39","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1007\/s12035-020-02166-z","volume":"58","author":"N Balasubramanian","year":"2021","unstructured":"Balasubramanian N, Sagarkar S, Choudhary AG et al (2021) Epigenetic Blockade of hippocampal SOD2 via DNMT3b-Mediated DNA methylation: implications in mild traumatic brain Injury-Induced persistent oxidative damage. Mol Neurobiol 58:1162\u20131184. https:\/\/doi.org\/10.1007\/s12035-020-02166-z","journal-title":"Mol Neurobiol"},{"key":"4655_CR40","doi-asserted-by":"publisher","unstructured":"Lu J, Jiao Z, Yu Y et al (2018) Programming for increased expression of hippocampal GAD67 mediated the hypersensitivity of the hypothalamic-pituitary-adrenal axis in male offspring rats with prenatal ethanol exposure. Cell Death Dis 9. https:\/\/doi.org\/10.1038\/s41419-018-0663-1","DOI":"10.1038\/s41419-018-0663-1"},{"key":"4655_CR41","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-\u2206\u2206CT method. Methods 25:402\u2013408. https:\/\/doi.org\/10.1006\/meth.2001.1262","journal-title":"Methods"},{"key":"4655_CR42","unstructured":"Sancheti JS, Shaikh MF, Khatwani PF et al (2013) Development and validation of a HPTLC method for simultaneous Estimation of L-Glutamic acid and \u03b3-Aminobutyric acid in mice brain"},{"key":"4655_CR43","doi-asserted-by":"publisher","first-page":"2891","DOI":"10.1080\/10826070701588760","volume":"30","author":"CS Babu","year":"2007","unstructured":"Babu CS, Sunil AG, Vasanthi HR et al (2007) Development and validation of an HPTLC method for simultaneous Estimation of excitatory neurotransmitters in rat brain. J Liq Chromatogr Relat Technol 30:2891\u20132902. https:\/\/doi.org\/10.1080\/10826070701588760","journal-title":"J Liq Chromatogr Relat Technol"},{"key":"4655_CR44","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1007\/s10787-018-0502-0","volume":"27","author":"M Gautam","year":"2019","unstructured":"Gautam M, Ramanathan M (2019) Saponins of tribulus terrestris attenuated neuropathic pain induced with vincristine through central and peripheral mechanism. Inflammopharmacology 27:761\u2013772. https:\/\/doi.org\/10.1007\/s10787-018-0502-0","journal-title":"Inflammopharmacology"},{"key":"4655_CR45","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1007\/s12035-021-02597-2","volume":"59","author":"SN Awathale","year":"2022","unstructured":"Awathale SN, Waghade AM, Kawade HM et al (2022) Neuroplastic changes in the superior colliculus and hippocampus in Self-rewarding paradigm: importance of visual cues. Mol Neurobiol 59:890\u2013915. https:\/\/doi.org\/10.1007\/s12035-021-02597-2","journal-title":"Mol Neurobiol"},{"key":"4655_CR46","doi-asserted-by":"publisher","unstructured":"Kawade HM, Awathale SN, Subhedar NK, Kokare DM (2022) Neuropeptide S facilitates extinction of fear via modulation of mesolimbic dopaminergic circuitry. Neuropharmacology 221. https:\/\/doi.org\/10.1016\/j.neuropharm.2022.109274","DOI":"10.1016\/j.neuropharm.2022.109274"},{"key":"4655_CR47","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1021\/acschemneuro.6b00383","volume":"8","author":"KT Ngo","year":"2017","unstructured":"Ngo KT, Varner EL, Michael AC, Weber SG (2017) Monitoring dopamine responses to potassium ion and nomifensine by in vivo Microdialysis with online liquid chromatography at One-Minute resolution. ACS Chem Neurosci 8:329\u2013338. https:\/\/doi.org\/10.1021\/acschemneuro.6b00383","journal-title":"ACS Chem Neurosci"},{"key":"4655_CR48","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1111\/acer.12034","volume":"37","author":"GA Deehan","year":"2013","unstructured":"Deehan GA, Engleman EA, Ding Z et al (2013) Microinjections of acetaldehyde or salsolinol into the posterior ventral tegmental area increase dopamine release in the nucleus accumbens shell. Alcohol Clin Exp Res 37:722\u2013729. https:\/\/doi.org\/10.1111\/acer.12034","journal-title":"Alcohol Clin Exp Res"},{"key":"4655_CR49","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.pbb.2012.03.009","volume":"102","author":"S Shahidani","year":"2012","unstructured":"Shahidani S, Reisi P, Naghdi N et al (2012) Lesion of medial prefrontal cortex reduces morphine-induced extracellular dopamine level in the ventral tegmental area: A Microdialysis study in rats. Pharmacol Biochem Behav 102:77\u201381. https:\/\/doi.org\/10.1016\/j.pbb.2012.03.009","journal-title":"Pharmacol Biochem Behav"},{"key":"4655_CR50","doi-asserted-by":"publisher","first-page":"4748","DOI":"10.1016\/j.cub.2021.08.052","volume":"31","author":"MG Kutlu","year":"2021","unstructured":"Kutlu MG, Zachry JE, Melugin PR et al (2021) Dopamine release in the nucleus accumbens core signals perceived saliency. Curr Biol 31:4748\u20134761e8. https:\/\/doi.org\/10.1016\/j.cub.2021.08.052","journal-title":"Curr Biol"},{"key":"4655_CR51","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.brainresbull.2010.09.006","volume":"83","author":"J Orze\u0142-Gryglewska","year":"2010","unstructured":"Orze\u0142-Gryglewska J, Ku\u015bmierczak M, Jurkowlaniec E (2010) Involvement of GABAergic transmission in the midbrain ventral tegmental area in the regulation of hippocampal theta rhythm. Brain Res Bull 83:310\u2013320. https:\/\/doi.org\/10.1016\/j.brainresbull.2010.09.006","journal-title":"Brain Res Bull"},{"key":"4655_CR52","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.nlm.2005.12.008","volume":"86","author":"DJ Berlau","year":"2006","unstructured":"Berlau DJ, McGaugh JL (2006) Enhancement of extinction memory consolidation: the role of the noradrenergic and GABAergic systems within the basolateral amygdala. Neurobiol Learn Mem 86:123\u2013132. https:\/\/doi.org\/10.1016\/j.nlm.2005.12.008","journal-title":"Neurobiol Learn Mem"},{"key":"4655_CR53","doi-asserted-by":"crossref","unstructured":"Sartorius A, Kiening KL, Kirsch P et al (2010) Remission of major depression under deep brain stimulation of the lateral Habenula in a Therapy-Refractory patient. Biol Psychiatry 67","DOI":"10.1016\/j.biopsych.2009.08.027"},{"key":"4655_CR54","doi-asserted-by":"publisher","unstructured":"Wang D, Li A, Dong K et al (2021) Lateral hypothalamus orexinergic inputs to lateral Habenula modulate maladaptation after social defeat stress. Neurobiol Stress 14. https:\/\/doi.org\/10.1016\/j.ynstr.2021.100298","DOI":"10.1016\/j.ynstr.2021.100298"},{"key":"4655_CR55","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/nature11527","volume":"491","author":"S Lammel","year":"2012","unstructured":"Lammel S, Lim BK, Ran C et al (2012) Input-specific control of reward and aversion in the ventral tegmental area. Nature 491:212\u2013217. https:\/\/doi.org\/10.1038\/nature11527","journal-title":"Nature"},{"key":"4655_CR56","doi-asserted-by":"publisher","unstructured":"Mukhara D, Banks ML, Neigh GN (2018) Stress as a risk factor for substance use disorders: A Mini-Review of molecular mediators. Front Behav Neurosci 12. https:\/\/doi.org\/10.3389\/fnbeh.2018.00309","DOI":"10.3389\/fnbeh.2018.00309"},{"key":"4655_CR57","doi-asserted-by":"crossref","unstructured":"Sharma S, Chawla S, Kumar P et al (2024) The chronic unpredictable mild stress (CUMS) paradigm: bridging the gap in depression research from bench to bedside. Brain Res 1843","DOI":"10.1016\/j.brainres.2024.149123"},{"key":"4655_CR58","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.neubiorev.2018.12.002","volume":"99","author":"S Antoniuk","year":"2019","unstructured":"Antoniuk S, Bijata M, Ponimaskin E, Wlodarczyk J (2019) Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neurosci Biobehav Rev 99:101\u2013116","journal-title":"Neurosci Biobehav Rev"},{"key":"4655_CR59","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.ynstr.2016.08.002","volume":"6","author":"P Willner","year":"2017","unstructured":"Willner P (2017) The chronic mild stress (CMS) model of depression: History, evaluation and usage. Neurobiol Stress 6:78\u201393","journal-title":"Neurobiol Stress"},{"key":"4655_CR60","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1159\/000087097","volume":"52","author":"P Willner","year":"2005","unstructured":"Willner P (2005) Chronic mild stress (CMS) revisited: consistency and Behavioural-Neurobiological concordance in the effects of CMS. Neuropsychobiology 52:90\u2013110. https:\/\/doi.org\/10.1159\/000087097","journal-title":"Neuropsychobiology"},{"key":"4655_CR61","doi-asserted-by":"publisher","unstructured":"Becker L, Mallien AS, Pfeiffer N et al (2023) Evidence-based severity assessment of the forced swim test in the rat. PLoS ONE 18. https:\/\/doi.org\/10.1371\/journal.pone.0292816","DOI":"10.1371\/journal.pone.0292816"},{"key":"4655_CR62","doi-asserted-by":"crossref","unstructured":"Trunnell ER, Baines J, Farghali S et al (2024) The need for guidance in antidepressant drug development: revisiting the role of the forced swim test and tail suspension test. Regul Toxicol Pharmacol 151","DOI":"10.1016\/j.yrtph.2024.105666"},{"key":"4655_CR63","doi-asserted-by":"publisher","first-page":"2898","DOI":"10.1016\/j.drudis.2021.08.003","volume":"26","author":"ER Trunnell","year":"2021","unstructured":"Trunnell ER, Carvalho C (2021) The forced swim test has poor accuracy for identifying novel antidepressants. Drug Discov Today 26:2898\u20132904","journal-title":"Drug Discov Today"},{"key":"4655_CR64","doi-asserted-by":"publisher","DOI":"10.3791\/52587","author":"R Yankelevitch-Yahav","year":"2015","unstructured":"Yankelevitch-Yahav R, Franko M, Huly A, Doron R (2015) The forced swim test as a model of depressive-like behavior. J Visualized Experiments 2015. https:\/\/doi.org\/10.3791\/52587","journal-title":"J Visualized Experiments 2015"},{"key":"4655_CR65","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1016\/j.jpsychires.2009.02.005","volume":"43","author":"M Thompson","year":"2009","unstructured":"Thompson M, Weickert CS, Wyatt E, Webster MJ (2009) Decreased glutamic acid decarboxylase67 mRNA expression in multiple brain areas of patients with schizophrenia and mood disorders. J Psychiatr Res 43:970\u2013977. https:\/\/doi.org\/10.1016\/j.jpsychires.2009.02.005","journal-title":"J Psychiatr Res"},{"key":"4655_CR66","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1017\/S1461145709990587","volume":"13","author":"B Karolewicz","year":"2010","unstructured":"Karolewicz B, MacIag D, O\u2019Dwyer G et al (2010) Reduced level of glutamic acid decarboxylase-67\u00a0kDa in the prefrontal cortex in major depression. Int J Neuropsychopharmacol 13:411\u2013420. https:\/\/doi.org\/10.1017\/S1461145709990587","journal-title":"Int J Neuropsychopharmacol"},{"key":"4655_CR67","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.neuron.2012.02.037","volume":"74","author":"SJ Shabel","year":"2012","unstructured":"Shabel SJ, Proulx CD, Trias A et al (2012) Input to the lateral Habenula from the basal ganglia is Excitatory, Aversive, and suppressed by serotonin. Neuron 74:475\u2013481. https:\/\/doi.org\/10.1016\/j.neuron.2012.02.037","journal-title":"Neuron"},{"key":"4655_CR68","doi-asserted-by":"publisher","unstructured":"Mitten EH, Souders A, Marron Fernandez de Velasco E, Wickman K (2024) Stress-induced anxiety-related behavior in mice is driven by enhanced excitability of ventral tegmental area GABA neurons. Front Behav Neurosci 18. https:\/\/doi.org\/10.3389\/fnbeh.2024.1425607","DOI":"10.3389\/fnbeh.2024.1425607"},{"key":"4655_CR69","doi-asserted-by":"publisher","unstructured":"Lowes DC, Chamberlin LA, Kretsge LN et al (2021) Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice. Nat Commun 12. https:\/\/doi.org\/10.1038\/s41467-021-23906-2","DOI":"10.1038\/s41467-021-23906-2"},{"key":"4655_CR70","doi-asserted-by":"publisher","unstructured":"Akhoondian M, Rashtiani S, Khakpour-Taleghani B et al (2023) Lateral Habenula deep brain stimulation alleviates depression-like behaviors and reverses the oscillatory pattern in the nucleus accumbens in an animal model of depression. Brain Res Bull 202. https:\/\/doi.org\/10.1016\/j.brainresbull.2023.110745","DOI":"10.1016\/j.brainresbull.2023.110745"},{"key":"4655_CR71","doi-asserted-by":"publisher","unstructured":"Zhang L, Hern\u00e1ndez VS, V\u00e1zquez-Ju\u00e1rez E et al (2016) Thirst is associated with suppression of Habenula output and active stress coping: is there a role for a Non-canonical Vasopressin-Glutamate pathway? https:\/\/doi.org\/10.3389\/fncir.2016.00013. Front Neural Circuits 10:","DOI":"10.3389\/fncir.2016.00013"},{"key":"4655_CR72","doi-asserted-by":"publisher","unstructured":"Zhang L, Hern\u00e1ndez VS, Swinny JD et al (2018) A GABAergic cell type in the lateral Habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling. Transl Psychiatry 8. https:\/\/doi.org\/10.1038\/s41398-018-0099-5","DOI":"10.1038\/s41398-018-0099-5"},{"key":"4655_CR73","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01192-1","author":"A Tchenio","year":"2017","unstructured":"Tchenio A, Lecca S, Valentinova K, Mameli M (2017) Limiting habenular hyperactivity ameliorates maternal separation-driven depressive-like symptoms. Nat Commun 8. https:\/\/doi.org\/10.1038\/s41467-017-01192-1","journal-title":"Nat Commun 8"},{"key":"4655_CR74","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1111\/cns.14106","volume":"29","author":"F Zhou","year":"2023","unstructured":"Zhou F, Wang D, Li H et al (2023) Orexinergic innervations at GABAergic neurons of the lateral Habenula mediates the anesthetic potency of Sevoflurane. CNS Neurosci Ther 29:1332\u20131344. https:\/\/doi.org\/10.1111\/cns.14106","journal-title":"CNS Neurosci Ther"},{"key":"4655_CR75","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/s41593-020-0617-7","volume":"23","author":"ME Flanigan","year":"2020","unstructured":"Flanigan ME, Aleyasin H, Li L et al (2020) Orexin signaling in GABAergic lateral Habenula neurons modulates aggressive behavior in male mice. Nat Neurosci 23:638\u2013650. https:\/\/doi.org\/10.1038\/s41593-020-0617-7","journal-title":"Nat Neurosci"},{"key":"4655_CR76","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1038\/s41380-024-02476-x","volume":"29","author":"N Song","year":"2024","unstructured":"Song N, Liu Z, Gao Y et al (2024) NAc-DBS corrects depression-like behaviors in CUMS mouse model via disinhibition of DA neurons in the VTA. Mol Psychiatry 29:1550\u20131566. https:\/\/doi.org\/10.1038\/s41380-024-02476-x","journal-title":"Mol Psychiatry"},{"key":"4655_CR77","doi-asserted-by":"publisher","unstructured":"Casquero-Veiga M, Bueno-Fernandez C, Romero-Miguel D et al (2021) Exploratory study of the long-term footprint of deep brain stimulation on brain metabolism and neuroplasticity in an animal model of obesity. Sci Rep 11. https:\/\/doi.org\/10.1038\/s41598-021-82987-7","DOI":"10.1038\/s41598-021-82987-7"},{"key":"4655_CR78","doi-asserted-by":"publisher","first-page":"e294","DOI":"10.1016\/j.wneu.2020.05.029","volume":"140","author":"M Wang","year":"2020","unstructured":"Wang M, Jia L, Wu X et al (2020) Deep brain stimulation improves motor function in rats with spinal cord injury by increasing synaptic plasticity. World Neurosurg 140:e294\u2013e303. https:\/\/doi.org\/10.1016\/j.wneu.2020.05.029","journal-title":"World Neurosurg"},{"key":"4655_CR79","doi-asserted-by":"publisher","first-page":"85","DOI":"10.22074\/cellj.2021.7139","volume":"23","author":"R Rohani","year":"2021","unstructured":"Rohani R, Aliaghaei A, Abdollahifar MA et al (2021) Long-term effects of hippocampal low-frequency stimulation on pro-inflammatory factors and astrocytes activity in kindled rats. Cell J 23:85\u201392. https:\/\/doi.org\/10.22074\/cellj.2021.7139","journal-title":"Cell J"},{"key":"4655_CR80","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s11427-023-2406-3","volume":"67","author":"CK Zhang","year":"2024","unstructured":"Zhang CK, Wang P, Ji YY et al (2024) Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain. Sci China Life Sci 67:67\u201382. https:\/\/doi.org\/10.1007\/s11427-023-2406-3","journal-title":"Sci China Life Sci"},{"key":"4655_CR81","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.biopsych.2005.09.018","volume":"59","author":"EJ Nestler","year":"2006","unstructured":"Nestler EJ, Carlezon WA (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59:1151\u20131159","journal-title":"Biol Psychiatry"},{"key":"4655_CR82","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s002130000420","volume":"150","author":"V Di Matteo","year":"2000","unstructured":"Di Matteo V, Di Mascio M, Di Giovanni G, Esposito E (2000) Acute administration of amitriptyline and Mianserin increases dopamine release in the rat nucleus accumbens: possible involvement of serotonin(2\u00a0C) receptors. Psychopharmacology 150:45\u201351. https:\/\/doi.org\/10.1007\/s002130000420","journal-title":"Psychopharmacology"},{"key":"4655_CR83","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.brainres.2017.07.021","volume":"1672","author":"YC Chen","year":"2017","unstructured":"Chen YC, Shi L, Zhu GY et al (2017) Effects of anterior thalamic nuclei deep brain stimulation on neurogenesis in epileptic and healthy rats. Brain Res 1672:65\u201372. https:\/\/doi.org\/10.1016\/j.brainres.2017.07.021","journal-title":"Brain Res"},{"key":"4655_CR84","doi-asserted-by":"crossref","unstructured":"Joffe RT, Uhde TW, Post RM, Minichiello MD (1987) Motor activity in depressed patients. Treated with Carbamazepine","DOI":"10.1016\/0006-3223(87)90003-5"},{"key":"4655_CR85","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.neuropharm.2017.01.015","volume":"116","author":"T Wang","year":"2017","unstructured":"Wang T, Zhang L, Zhang QJ et al (2017) Involvement of lateral Habenula \u03b11 subunit-containing GABAA receptor-mediated inhibitory transmission in the regulation of depression-related behaviors in experimental parkinson\u2019s disease. Neuropharmacology 116:399\u2013411. https:\/\/doi.org\/10.1016\/j.neuropharm.2017.01.015","journal-title":"Neuropharmacology"},{"key":"4655_CR86","doi-asserted-by":"publisher","unstructured":"Han YX, Tao C, Gao XR et al (2018) BDNF-Related imbalance of Copine 6 and synaptic plasticity markers couples with Depression-Like behavior and immune activation in CUMS rats. Front Neurosci 12. https:\/\/doi.org\/10.3389\/fnins.2018.00731","DOI":"10.3389\/fnins.2018.00731"},{"key":"4655_CR87","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.npbr.2012.06.003","volume":"18","author":"Y Zhao","year":"2012","unstructured":"Zhao Y, Liu LJ, Wang C, Li SX (2012) Swimming exercise May not alleviate the depressive-like behaviors and circadian alterations of neuroendocrine induced by chronic unpredictable mild stress in rats. Neurol Psychiatry Brain Res 18:202\u2013207. https:\/\/doi.org\/10.1016\/j.npbr.2012.06.003","journal-title":"Neurol Psychiatry Brain Res"}],"updated-by":[{"DOI":"10.1007\/s11064-026-04675-0","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000}}],"container-title":["Neurochemical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04655-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11064-025-04655-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04655-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T10:11:08Z","timestamp":1772619068000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11064-025-04655-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":87,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["4655"],"URL":"https:\/\/doi.org\/10.1007\/s11064-025-04655-w","relation":{},"ISSN":["0364-3190","1573-6903"],"issn-type":[{"value":"0364-3190","type":"print"},{"value":"1573-6903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"assertion":[{"value":"22 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised due to update in removal of duplicated author name in the author group.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2026","order":9,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":10,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":11,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s11064-026-04675-0","URL":"https:\/\/doi.org\/10.1007\/s11064-026-04675-0","order":12,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"36"}}