{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:15:00Z","timestamp":1791980100521,"version":"4.4.0"},"reference-count":59,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Pl19\/00170"],"award-info":[{"award-number":["Pl19\/00170"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-097534-B-I00"],"award-info":[{"award-number":["RTI2018-097534-B-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Depression is the most prevalent of the mental illnesses and serotonin (5-hydroxytryptamine, 5-HT) is considered to be the major neurotransmitter involved in its etiology and treatment. In this context, 5-HT1A receptors have attracted interest as targets for therapeutic intervention. Notably the activation of presynaptic 5-HT1A autoreceptors delays antidepressant effects whereas the stimulation of postsynaptic 5-HT1A heteroreceptors is needed for an antidepressant action. NLX-101 (also known as F15599) is a selective biased agonist which exhibits preferred activation of cortical over brain stem 5-HT1A receptors. Here, we used behavioral, neurochemical and molecular methods to examine the antidepressant-like effects in rats of a single dose of NLX-101 (0.16 mg\/kg, i.p.). NLX-101 reduced immobility in the forced swim test when measured 30 min but not 24 h after drug administration. NLX-101 increased extracellular concentrations of glutamate and dopamine in the medial prefrontal cortex, but no changes were detected in the efflux of noradrenaline or 5-HT. NLX-101 also produced an increase in the activation of pmTOR, pERK1\/2 and pAkt, and the expression of PSD95 and GluA1, which may contribute to its rapid antidepressant action.<\/jats:p>","DOI":"10.3390\/ph15030337","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T20:19:10Z","timestamp":1646943550000},"page":"337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Molecular Signaling Mechanisms for the Antidepressant Effects of NLX-101, a Selective Cortical 5-HT1A Receptor Biased Agonist"],"prefix":"10.3390","volume":"15","author":[{"given":"Sharon","family":"Cabanu","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria (IBBTEC), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Cantabria, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1229-001X","authenticated-orcid":false,"given":"Fuencisla","family":"Pilar-Cu\u00e9llar","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria (IBBTEC), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Zubakina","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria (IBBTEC), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Cantabria, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5045-7680","authenticated-orcid":false,"given":"Eva","family":"Florensa-Zanuy","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria (IBBTEC), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia","family":"Senserrich","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria (IBBTEC), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-5714","authenticated-orcid":false,"given":"Adrian","family":"Newman-Tancredi","sequence":"additional","affiliation":[{"name":"Neurolixis SAS, 2 Rue Georges Charpak, 81100 Castres, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0570-4931","authenticated-orcid":false,"given":"Albert","family":"Adell","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria (IBBTEC), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1176\/ajp.2006.163.11.1905","article-title":"Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report","volume":"163","author":"Rush","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2013.10.043","article-title":"Treatment-resistant depression: Definitions, review of the evidence, and algorithmic approach","volume":"156","author":"McIntyre","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jad.2018.06.045","article-title":"The burden of treatment-resistant depression: A systematic review of the economic and quality of life literature","volume":"242","author":"Johnston","year":"2019","journal-title":"J. Affect. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0006-3223(99)00230-9","article-title":"Antidepressant effects of ketamine in depressed patients","volume":"47","author":"Berman","year":"2000","journal-title":"Biol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1001\/archpsyc.63.8.856","article-title":"A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression","volume":"63","author":"Zarate","year":"2006","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00213-013-3024-x","article-title":"Ketamine elicits sustained antidepressant-like activity via a serotonin-dependent mechanism","volume":"228","author":"Gigliucci","year":"2013","journal-title":"Psychopharmacology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/npp.2015.233","article-title":"The antidepressant effects of an mGlu2\/3 receptor antagonist and ketamine require AMPA receptor stimulation in the mPFC and subsequent activation of the 5-HT neurons in the DRN","volume":"41","author":"Fukumoto","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1007\/s00213-016-4327-5","article-title":"Differential interaction with the serotonin system by S-ketamine, vortioxetine, and fluoxetine in a genetic rat model of depression","volume":"233","author":"Liebenberg","year":"2016","journal-title":"Psychopharmacology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/ijnp\/pyx116","article-title":"Role of 5-HT1A receptor stimulation in the medial prefrontal cortex in the sustained antidepressant effects of ketamine","volume":"21","author":"Fukumoto","year":"2018","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0893-133X(96)00242-4","article-title":"Selective activation of postsynaptic 5-HT1A receptors induces rapid antidepressant response","volume":"16","author":"Blier","year":"1997","journal-title":"Neuropsychopharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10150","DOI":"10.1523\/JNEUROSCI.18-23-10150.1998","article-title":"Long-term antidepressant treatments result in a tonic activation of forebrain 5-HT1A receptors","volume":"18","author":"Haddjeri","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1017\/S1461145709991222","article-title":"F15599, a highly selective post-synaptic 5-HT1A receptor agonist: In-vivo profile in behavioural models of antidepressant and serotonergic activity","volume":"13","author":"Assie","year":"2010","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1021\/acschemneuro.7b00443","article-title":"Activity of serotonin 5-HT1A receptor biased agonists in rat: Anxiolytic and antidepressant-like properties","volume":"9","author":"Partyka","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1177\/0269881119860666","article-title":"Cortical 5-hydroxytryptamine 1A receptor biased agonist, NLX-101, displays rapid-acting antidepressant-like properties in the rat chronic mild stress model","volume":"33","author":"Papp","year":"2019","journal-title":"J. Psychopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1007\/s00213-021-05849-0","article-title":"The selective 5-HT1A receptor biased agonists, F15599 and F13714, show antidepressant-like properties after a single administration in the mouse model of unpredictable chronic mild stress","volume":"238","author":"Gawalska","year":"2021","journal-title":"Psychopharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113082","DOI":"10.1016\/j.bbr.2020.113082","article-title":"NLX-101, a highly selective 5-HT1A receptor biased agonist, mediates antidepressant-like activity in rats via prefrontal cortex 5-HT1A receptors","volume":"401","author":"Auclair","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1111\/j.1476-5381.2010.00738.x","article-title":"Preferential in vivo action of F15599, a novel 5-HT1A receptor agonist, at postsynaptic 5-HT1A receptors","volume":"160","author":"Artigas","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109832","DOI":"10.1016\/j.pnpbp.2019.109832","article-title":"Activation of 5-HT1A postsynaptic receptors by NLX-101 results in functional recovery and an increase in neuroplasticity in mice with brain ischemia","volume":"99","author":"Aguiar","year":"2019","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.neuropharm.2008.09.004","article-title":"Region-specific changes in 5-HT1A agonist-induced extracellular signal-regulated kinases 1\/2 phosphorylation in rat brain: A quantitative ELISA study","volume":"56","author":"Buritova","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/BF02245592","article-title":"Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants","volume":"121","author":"Detke","year":"1995","journal-title":"Psychopharmacology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1097\/00008877-199711000-00010","article-title":"The forced swimming test as a model for core and component behavioral effects of antidepressant drugs","volume":"8","author":"Lucki","year":"1997","journal-title":"Behav. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.physbeh.2014.01.037","article-title":"Individual differences in the forced swimming test and neurochemical kinetics in the rat brain","volume":"128","year":"2014","journal-title":"Physiol. Behav."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/BF02244785","article-title":"Increase of extracellular dopamine in the prefrontal cortex: A trait of drugs with antidepressant potential?","volume":"115","author":"Tanda","year":"1994","journal-title":"Psychopharmacology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10831","DOI":"10.1523\/JNEUROSCI.2999-05.2005","article-title":"Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: Role in atypical antipsychotic action","volume":"25","author":"Scorza","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1093\/cercor\/bhr220","article-title":"5-HT1A receptor agonists enhance pyramidal cell firing in prefrontal cortex through a preferential action on GABA interneurons","volume":"22","author":"Santana","year":"2012","journal-title":"Cereb. Cortex"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/nn1103","article-title":"Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission","volume":"6","author":"Floresco","year":"2003","journal-title":"Nat. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1523\/JNEUROSCI.20-10-03864.2000","article-title":"Projections from the rat prefrontal cortex to the ventral tegmental area: Target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons","volume":"20","author":"Carr","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/S0006-3223(99)00236-X","article-title":"Reciprocal changes in prefrontal and limbic dopamine responsiveness to aversive and rewarding stimuli after chronic mild stress: Implications for the psychobiology of depression","volume":"46","author":"Loddo","year":"1999","journal-title":"Biol. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1001\/archpsyc.64.3.327","article-title":"The role of dopamine in the pathophysiology of depression","volume":"64","author":"Dunlop","year":"2007","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1124\/jpet.116.233627","article-title":"The rapidly acting antidepressant ketamine and the mGlu2\/3 receptor antagonist LY341495 rapidly engage dopaminergic mood circuits","volume":"358","author":"Witkin","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1007\/s00213-017-4651-4","article-title":"Dopaminergic mechanisms in memory consolidation and antidepressant reversal of a chronic mild stress-induced cognitive impairment","volume":"234","author":"Papp","year":"2017","journal-title":"Psychopharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature11740","article-title":"Dopamine neurons modulate neural encoding and expression of depression-related behaviour","volume":"493","author":"Tye","year":"2013","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1523\/JNEUROSCI.17-08-02921.1997","article-title":"Activation of glutamatergic neurotransmission by ketamine: A novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex","volume":"17","author":"Moghaddam","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1017\/S1461145711001064","article-title":"Importance of inter-hemispheric prefrontal connection in the effects of non-competitive NMDA receptor antagonists","volume":"15","author":"Campa","year":"2012","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1021\/acschemneuro.9b00288","article-title":"Role of serotonin and noradrenaline in the rapid antidepressant action of ketamine","volume":"10","author":"Campa","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.biopsych.2007.05.028","article-title":"Cellular mechanisms underlying the antidepressant effects of ketamine: Role of \u03b1-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors","volume":"63","author":"Maeng","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1503\/jpn.160175","article-title":"Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism","volume":"42","author":"Aleksandrova","year":"2017","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"172913","DOI":"10.1016\/j.pbb.2020.172913","article-title":"Cortical and raphe GABAA, AMPA receptors and glial GLT-1 glutamate transporter contribute to the sustained antidepressant activity of ketamine","volume":"192","author":"Pham","year":"2020","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1126\/science.1190287","article-title":"mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists","volume":"329","author":"Li","year":"2010","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1126\/science.1222939","article-title":"Synaptic dysfunction in depression: Potential therapeutic targets","volume":"338","author":"Duman","year":"2012","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nm.4050","article-title":"Synaptic plasticity and depression: New insights from stress and rapid-acting antidepressants","volume":"22","author":"Duman","year":"2016","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.tips.2021.08.003","article-title":"Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics","volume":"42","author":"Aleksandrova","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.1476-5381.2008.00001.x","article-title":"Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist","volume":"156","author":"Martel","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jpsychires.2014.04.010","article-title":"MAPK signaling correlates with the antidepressant effects of ketamine","volume":"55","author":"Vieira","year":"2014","journal-title":"J. Psychiatr. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.tips.2020.04.004","article-title":"Modulation of ion channels and receptors by p11 (S100A10)","volume":"41","author":"Seo","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.1117571","article-title":"Alterations in 5-HT1B receptor function by p11 in depression-like states","volume":"311","author":"Svenningsson","year":"2006","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1038\/mp.2016.118","article-title":"Cellular and molecular basis for stress-induced depression","volume":"22","author":"Seo","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrn3564","article-title":"p11 and its role in depression and therapeutic responses to antidepressants","volume":"14","author":"Svenningsson","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1038\/s41380-019-0400-x","article-title":"Neurobiology of rapid-acting antidepressants: Convergent effects on GluA1-synaptic function","volume":"24","author":"Duman","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1017\/S1461145709990575","article-title":"Aberrant extracellular signal-regulated kinase (ERK)1\/2 signalling in suicide brain: Role of ERK kinase 1 (MEK1)","volume":"12","author":"Dwivedi","year":"2009","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.pnpbp.2011.05.010","article-title":"The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder","volume":"35","author":"Jernigan","year":"2011","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1017\/S1461145712000016","article-title":"Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects","volume":"16","author":"Duric","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0361-9230(02)00859-6","article-title":"Effects of single or repeated restraint stress on GluR1 and GluR2 flip and flop mRNA expression in the hippocampal formation","volume":"59","author":"Rosa","year":"2002","journal-title":"Brain Res. Bull."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/j.1471-4159.2008.05642.x","article-title":"Age-dependent effects of chronic stress on brain plasticity and depressive behavior","volume":"107","author":"Toth","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature10130","article-title":"NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses","volume":"475","author":"Autry","year":"2011","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/da.22501","article-title":"Ketamine\u2019s mechanism of action: A path to rapid-acting antidepressants","volume":"33","author":"Abdallah","year":"2016","journal-title":"Depress. Anxiety"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2174\/1570159X14666160309114549","article-title":"Molecular and cellular mechanisms of rapid-acting antidepressants ketamine and scopolamine","volume":"15","author":"Wohleb","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0165-6147(02)02017-5","article-title":"Assessing antidepressant activity in rodents: Recent developments and future needs","volume":"23","author":"Cryan","year":"2002","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_59","unstructured":"Paxinos, G., and Watson, C. (2008). The Rat Brain in Stereotaxic Coordinates, Academic Press."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/3\/337\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:34:22Z","timestamp":1760135662000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/3\/337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,10]]},"references-count":59,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ph15030337"],"URL":"https:\/\/doi.org\/10.3390\/ph15030337","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,10]]}}}