Skip to main content

Advertisement

SpringerLink
Log in

Neuroanatomical, Biochemical, and Functional Modifications in Brain Induced by Treatment with Antidepressants

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Depression is a psychosomatic disorder. The pharmacological treatment of depression has been based on the pathophysiology of deficiency in monoamines, mainly serotonin and noradrenaline. All approved antidepressants designed to enhance central monoaminergic tone possess many limitations such as 2 to 5 weeks delay in response, a limited clinical efficacy, and severe side effects. Since the pathophysiological aberrations associated to depression go beyond monoamines, the development of better antidepressants would depend on the identification and understanding of new cellular targets. The pharmacological studies of antidepressants, however, indicate the involvement of the blockade of neuronal uptake systems for norepinephrine and serotonin (5-hydroxytryptamine) including receptors for neurotransmitters. Many preclinical studies have suggested that hippocampus containing abundant agonists such as5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG) is critically involved in the mechanism of action of antidepressants. DG being a part of hippocampus possibly contributes to the brain functions such as formation of new sporadic memories. It is reported that antidepressants cause significant alterations in the structure and function of different brain regions in order to finally lead to their therapeutic effects. This review presents an overview of structural changes in the brain during depression; different neurobiological theories and novel drug development; strategy of augmentation with combinatorial therapy; receptors and targets of actions of antidepressants; and involvement of key signaling factors in the regulation of depression, pharmacology, metabolism, and the underlying principles involved in displaying how the application of antidepressants modulates the structure and function of the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

Not applicable.

Code Availability

Not applicable.

References

  1. Murray CJ, Lopez AD (1996) Evidence-based health policy–lessons from the global burden of disease study. Science 274(5288):740–743

    Article  CAS  PubMed  Google Scholar 

  2. Smith K (2014) Mental health: a world of depression. Nature 515(7526):181

    Article  PubMed  CAS  Google Scholar 

  3. Khushboo, Sharma, B. (2017) Antidepressants: mechanism of action, toxicity and possible amelioration. J Appl Biotech & Bioeng. 3 (5): 437-448

  4. Khushboo, Sharma, B. (2019) Factors inducing depression as effective tool in therapy. Medical and Clinical Archives. 3:1–4 https://doi.org/10.15761/MCA.1000163

  5. Gupta, VK, Sharma, B. (2016) Modulations of mammalian brain functions by antidepressant drugs: role of some phytochemicals as prospective antidepressants. Evidence based medicine and practice. 1(3),1000003:1–12

  6. Khushboo, Sharma, B. (2020) Neurochemical signaling in psychosomatic disorders with special reference to depression: impact of target-based pharmaceuticals, neurochemical systems and signaling: from molecules to networks.(Eds. Sahab Uddin) CRC Press, a Taylor & Francis Group. (In Press)

  7. Wood JG, Joyce PR, Miller AL, Mulder RT, Kennedy MA (2002) A polymorphism in the dopamine beta-hydroxylase gene is associated with “paranoid ideation” in patients with major depression. Biol Psychiatry 51(5):365–369. https://doi.org/10.1016/s0006-3223(01)01367-1

    Article  CAS  PubMed  Google Scholar 

  8. Matthes S, Mosienko V, Bashammakh S, Alenina N, Bader M (2010) Tryptophan hydroxylase as novel target for the treatment of depressive disorders. Pharmacology 85:95–109. https://doi.org/10.1159/000279322

    Article  CAS  PubMed  Google Scholar 

  9. Jope RS (2011) Glycogen synthase kinase-3 in the etiology and treatment of mood disorders. Front Mol Neurosci 4:16. https://doi.org/10.3389/fnmol.2011.00016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Almas, A., Forsell, Y., Millischer, V., Möller, J., Lavebratt. (2018) C. Association of Catechol-O-methyltransferase (COMT Val158Met) with future risk of cardiovascular disease in depressed individuals - a Swedish population-based cohort study. BMC Med Genet. 19(1):126. https://doi.org/10.1186/s12881-018-0645-2.

  11. Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS (2000) Hippocampal volume reduction in major depression. Am J Psychiatry 157(1):115–118. https://doi.org/10.1176/ajp.157.1.115

    Article  CAS  PubMed  Google Scholar 

  12. Westenberg, HG. (1999) Pharmacology of antidepressants: selectivity or multiplicity? J Clin Psychiatry. 60(17); 4–8; discussion 46–8.

  13. Khushboo, Sharma B. (2017) Antidepressants: mechanism of action, toxicity and possible amelioration. J Appl Biotechnol Bioeng., 3(5):437-448 https://doi.org/10.15406/jabb.2017.03.00082

  14. Standaert. (2005) Harvard-MIT division of health sciences and technology. Neuropharmacology II Antidepressants and Sedatives. USA. p. 1–8

  15. Bunney WE, Davis JM (1965) Norepinephrine in depressive reactions. Arch Gen Psychiatry 13(6):483–494

    Article  CAS  PubMed  Google Scholar 

  16. Heninger GR, Delgado PL, Charney DS (1996) The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans. Pharmacopsychiatry 29(1):2–11

    Article  CAS  PubMed  Google Scholar 

  17. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 122(5):509–522

    Article  CAS  PubMed  Google Scholar 

  18. Fournier NM, Duman RS (2012) Role of vascular endothelial growth factor in adult hippocampal neurogenesis: implications for the pathophysiology and treatment of depression. Behav Brain Res 227(2):440–449. https://doi.org/10.1016/j.bbr.2011.04.022

    Article  CAS  PubMed  Google Scholar 

  19. Anlar B, Oktem F, Bakkaloglu B, Haliloglu M, Oguz H, Unal F, Pehlivanturk B, Gokler B, Ozbesler C, Yordam N (2007) Urinary epidermal and insulin-like growth factor excretion in autistic children. Neuropediatrics 38:151–153

    Article  CAS  PubMed  Google Scholar 

  20. Palazidou E (2012) The neurobiology of depression. Br Med Bull 101:127–145. https://doi.org/10.1093/bmb/lds004

    Article  CAS  PubMed  Google Scholar 

  21. Rice, F. (2010) Genetics of childhood and adolescent depression: insights into etiological heterogeneity and challenges for future genomic research. Genome Medicine. 2, Article number: 68. https://doi.org/10.1186/gm189

  22. Saveanu RV, Nemeroff CB (2012) Etiology of depression: genetic and environmental factors. Psychiatr Clin North Am 35(1):51–71. https://doi.org/10.1016/j.psc.2011.12.001

    Article  PubMed  Google Scholar 

  23. Kessler RC, Bromet EJ (2013) The epidemiology of depression across cultures. Annu Rev Public Health 34:119–138

    Article  PubMed  PubMed Central  Google Scholar 

  24. Dusi N, Stefano Barlati S, Vita A, Brambilla P (2015) Brain structural effects of antidepressant treatment in major depression. CurrNeuropharmacol 13(4):458–465. https://doi.org/10.2174/1570159X1304150831121909

    Article  CAS  Google Scholar 

  25. Zuccoli GS, Saia-Cereda VM, Nascimento JM, Martins-de-Souza D (2017) The energy metabolism dysfunction in psychiatric disorders postmortem brains: focus on proteomic Evidence. Front Neurosci 11:493. https://doi.org/10.3389/fnins.2017.00493

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kennedy SH, Evans KR, Krüger S, Mayberg HS, Meyer JH, McCann S, Vaccarino FJ (2001) Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry 158(6):899–905. https://doi.org/10.1176/appi.ajp.158.6.899

    Article  CAS  PubMed  Google Scholar 

  27. Van Heeringen K, Wu GR, Vervaet M, Vanderhasselt MA, Baeken C (2017) Decreased resting state metabolic activity in frontopolar and parietal brain regions is associated with suicide plans in depressed individuals. J Psychiatr Res 84:243–248. https://doi.org/10.1016/j.jpsychires.2016.10.011

    Article  PubMed  Google Scholar 

  28. Zhang FF, Peng W, Sweeney JA, Jia ZY, Gong QY (2018) Brain structure alterations in depression: psychoradiological evidence. CNS Neurosci Ther 24(11):994–1003. https://doi.org/10.1111/cns.12835

    Article  PubMed  PubMed Central  Google Scholar 

  29. Burker EJ, Evon DM, Marroquin Loiselle M, Finkel JB, Mill MR (2005) Coping predicts depression and disability in heart transplant candidates. J Psychoso Res 59:215–222

    Article  Google Scholar 

  30. Bodkin JA, Zornberg GL, Lukas SE, Cole JO (1995) Buprenorphine treatment of refractory depression. J Clin Psychopharmacol 15:49–57

    Article  CAS  PubMed  Google Scholar 

  31. Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78:189–225

    Article  CAS  PubMed  Google Scholar 

  32. Beaulieu JM, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63:182–217

    Article  CAS  PubMed  Google Scholar 

  33. Ford CP (2014) The role of D2-autoreceptors in regulating dopamine neuron activity and transmission. Neuroscience 282:13–22. https://doi.org/10.1016/j.neuroscience.2014.01.025

    Article  CAS  PubMed  Google Scholar 

  34. Fernandez-Teruel A, Escorihuela RM, Boix F, Longoni B, Corda MG, Tobena A (1990) Imipramine and desipramine decrease the GABA-stimulated chloride uptake, and antigabaergic agents enhance their action in the forced swimming test in rats. Neuropsychobiol 23:147–152

    Article  CAS  Google Scholar 

  35. Linde K, Berner MM, Kriston L. (2008) St John’s Wort for major depression. Cochrane Database Syst Rev. CD000448.

  36. Ernst E (2009) Review: St John’s Wort superior to placebo and similar to antidepressants for major depression but with fewer side effects. Evid Based Ment Health 12:78

    Article  PubMed  Google Scholar 

  37. Wang SM, Han C, Bahk WM, Lee SJ, Patkar AA, Masand PS, Pae CU (2018) Addressing the side effects of contemporary antidepressant drugs: a comprehensive review. Chonnam Med J 54(2):101–112. https://doi.org/10.4068/cmj.2018.54.2.101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Goss AJ, Kaser M, Costafreda SG, Sahakian BJ, Fu CH (2013) Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry 74:1101–1107

    Article  CAS  PubMed  Google Scholar 

  39. Lam RW, Wan DD, Cohen NL, Kennedy SH (2002) Combining antidepressants for treatment-resistant depression: a review. J Clin Psychiatry 63:685–693

    Article  CAS  PubMed  Google Scholar 

  40. DeBattista C, Lembke A (2005) Update on augmentation of antidepressant response in resistant depression. Curr Psychiatry Rep 7:435–440

    Article  PubMed  Google Scholar 

  41. Trivedi MH, Fava M, Marangell LB, Osser DN, Richard C, Shelton RC (2006) Use of treatment algorithms for depression. Prim Care Companion J Clin Psychiatry 8(5):291–298. https://doi.org/10.4088/pcc.v08n0506

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kirsch I (2014) Antidepressants and the placebo effect. Z Psychol 222(3):128–134. https://doi.org/10.1027/2151-2604/a000176

    Article  PubMed  PubMed Central  Google Scholar 

  43. Wang JW, David DJ, Monckton JE, Battaglia F, Hen R (2008) Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci 28:1374–1384. https://doi.org/10.1523/JNEUROSCI.3632-07.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Adell A, Castro E, Celada P, Bortolozzi A, Pazos A, Artigas F (2005) Strategies for producing faster acting antidepressants. Drug Discov Today 10:578–585

    Article  CAS  PubMed  Google Scholar 

  45. Schechter LE, Rin RH, Beyer CE, Hughes ZA, Khawaja X, Malberg JE (2005) Innovative approaches for the development of antidepressant drugs: current and future strategies. NeuroRx 2:590–611

    Article  PubMed  PubMed Central  Google Scholar 

  46. Mann, JJ, Arango V, Marzuk P.M, Theccanat S, Reis DJ. (1989) Evidence for the 5-HT hypothesis of suicide. A review of post-mortem studies. Br J Psychiatry, Suppl. Dec;(8):7–14.

  47. Pandey GN (1997) Altered serotonin functions in suicide. Evidence from platelet and neuroendocrine studies. Ann N Y Acad Sci 836:182–200

    Article  CAS  PubMed  Google Scholar 

  48. Waeber C, Sebben M, Nieoullon A, Bockaert J, Dumuis A (1994) Re-gional distribution and ontogeny of 5-HT4 binding sites in rodent brain. Neuropharmacology 33:527–541

    Article  CAS  PubMed  Google Scholar 

  49. Vilaro MT, Cortes R, Mengod G (2005) Serotonin 5-HT4 receptors and their mRNAs in rat and guinea pig brain: distribution and effects of neurotoxic lesions. J Comp Neurol 484:418–439

    Article  CAS  PubMed  Google Scholar 

  50. Hoyer D, Hannon JP, Martin GR (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. PharmacolBiochemBehav 71:533–554

    CAS  Google Scholar 

  51. Andrade R, Chaput Y (1991) 5-Hydroxytryptamine4-like receptors mediate the slow excitatory response to serotonin in the rat hippocampus. J Pharmacol Exp Ther 257:930–937

    CAS  PubMed  Google Scholar 

  52. Fagni L, Dumuis A, Sebben M, Bockaert J (1992) The 5-HT4 receptor subtype inhibits K+ current in colliculi neurones via activation of a cyclic AMP-dependent protein kinase. Br J Pharmacol 105:973–979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Eglen RM, Wong EH, Dumuis A, Bockaert J (1995) Central 5-HT4 receptors. Trends Pharmacol Sci 16:391–398

    Article  CAS  PubMed  Google Scholar 

  54. Vidal R, Pilar-Cuéllar F, dos Anjos S, Linge R, Treceñ B, Inés Vargas V, Rodriguez-Gaztelumendi A, Mostany R, Castro E, Diaz A, Valdizán EM, Pazo A. (2011) New strategies in the development of antidepressants: towards the modulation of Sulser F: mode of action of antidepressant drugs. J Clin Psychiatry. 44 (No.5, Sec. 2):14–20, 1983

  55. Gershon MD (2004) Review article: serotonin receptors and transporters: roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther 7:3–14

    Article  Google Scholar 

  56. Kaumann AJ, Levy FO (2006) 5-hydroxytryptamine receptors in the human cardiovascular system. PharmacolTher 111:674–706

    CAS  Google Scholar 

  57. Matsumoto M, Togashi H, Mori K et al (2001) Evidence for involvement of central 5-HT4 receptors in cholinergic function associated with cognitive processes: behavioral, electrophysiological, and neuro- chemical studies. J Pharmacol Exp Ther 296:676–682

    CAS  PubMed  Google Scholar 

  58. Manuel-Apolinar L, Rocha L, Pascoe D, Castillo E, Castillo C, Meneses A (2005) Modifications of 5-HT4 receptor expression in rat brain during memory consolidation. Brain Res 1042:73–81

    Article  CAS  PubMed  Google Scholar 

  59. Jean A, Conductier G, Manrique C et al (2007) Anorexia induced by activation of serotonin 5-HT4 receptors is mediated by increases in CART in the nucleus accumbens. Proc Natl Acad Sci USA 104:16335–16340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lucas G, Rymar VV, Du J et al (2007) Serotonin (4) (5-HT (4)) receptor agonists are putative antidepressants with a rapid onset of action. Neuron 55:712–725

    Article  CAS  PubMed  Google Scholar 

  61. Rosel P, Arranz B, Urretavizcaya M, Oros M, San L, Navarro MA (2004) Altered 5-HT2A and 5-HT4 postsynaptic receptors and their intracel- lular signalling systems IP3 and cAMP in brains from depressed violent suicide victims. Neuropsychobiology 49:189–195

    Article  CAS  PubMed  Google Scholar 

  62. Lucas G, Compan V, Charnay Y et al (2005) Frontocortical 5-HT4 receptors exert positive feedback on serotonergic activity: viral transfect-ions, subacute and chronic treatments with 5-HT4 agonists. Biol Psychiatry 57:918–925

    Article  CAS  PubMed  Google Scholar 

  63. Vidal R, Pilar-Cuéllar F, dos Anjos S, Linge R, Treceño B, Inés Vargas V, Rodriguez-Gaztelumendi A, Mostany R, Castro E, Diaz A, Valdizán EM, Pazo A (2011) New strategies in the development of antidepressants: towards the modulation of neuroplasticity pathways. CurrPharmaceu Des 17:521–533

    CAS  Google Scholar 

  64. Tamburella A, Micale V, Navarria A, Drago F (2009) Antidepressant properties of the 5-HT4 receptor partial agonist, SL65.0155: behavioral and neurochemical studies in rats. Prog Neuro- PsychopharmacolBiol Psychiatr 33:1205–1210

    Article  CAS  Google Scholar 

  65. Pascual-Brazo J, Castro E, Díaz A. et al. (2010) A 7-day treatment with the 5-HT4 receptor agonist RS67333 is required to obtain a complete antidepressant-like response in animal models. Program No. 543.16. 2010 Neuroscience Meeting Planner. San Diego, CA, USA: Society for Neuroscience. Online.

  66. Vidal R, Valdizán EM, Mostany R, Pazos A, Castro E (2009) Long-term treatment with fluoxetine i., duces desensitization of 5-HT4 receptor-dependent signalling and functionality in rat brain. J Neurochem 110:1120–1127

    Article  CAS  PubMed  Google Scholar 

  67. Vidal R, Valdizán EM, Vilaró T, Pazos A, Castro E (2010) Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats. Br J Pharmacol 161:695–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Enna SJ. (2007) The GABA receptors. In: Enna SJ, Mohler H (eds). The GABA Receptors, 3rd edn. Humana Press: Totowa, NJ, pp. 1–21

  69. Bowery NG. Historical perspective and emergence of the GABAB receptor. In: Blackburn TP(ed.). GABAB receptor pharmacology: a tribute to Norman Bowery. Advances in pharmacology, 2010, Vol. 58.Academic Press: New York, pp. 1–18.

  70. Binet V, Goudet C, Brajon C, Le Corre L, Archer F, Pin J-P et al (2006) Molecular mechanisms of action of GABAB receptor activation: new insights from the mechanism of action of CGP7930, a positive allosteric modulator. Biochem Pharmacol 1068:109–117

    Google Scholar 

  71. Enna SJ, Bowery NG. (2010) GABAB receptor. In: Lennarz W, Lane MD (eds). Encyclopedia of Biological Chemistry, , Vol. 3. Elsevier: New York, in press.

  72. Farb DH, Steiger JL, Martin SC, Gravielle MC, Gibbs TT, Russek SJ. (2007) Mechanisms of GABAA and GABAB receptor gene regulation and cell surface expression. In: Enna SJ, Möhler H, editors. The GABA Receptors. Totowa: Humana Press;. pp. 169–238. https://doi.org/10.1007/978-1-59745-465-08

  73. Cryan JF, Slattery DA. (2010) GABAB receptors and depression: current status. In: Blackburn TP (ed.). GABAB receptor pharmacology: a tribute to Norman Bowery. Advances in pharmacology, Vol. 58. Academic Press: New York. pp. 427–451.

  74. Ferguson JM (2001) SSRI antidepressant medications: adverse effects and tolerability. Prim care companion J Clin Psychiatry 3(1):22–27. https://doi.org/10.4088/pcc.v03n0105

    Article  PubMed  PubMed Central  Google Scholar 

  75. Pytka K, Dziubina A, Młyniec K, Dziedziczak A, Elz˙ bieta Z˙ mudzk, Furgała A, Olczyk A, Sapa J, Filipek B. (2016) The role of glutamatergic, GABA-ergic, and cholinergic receptors in depression and antidepressant-like effect. Pharmacological Reports. 68: 443–450

  76. Ghose S, Winter MK, Mc Carson KE, Tamminga CA, Enna SJ (2011) The GABAB receptor as a target for antidepressant drug action. Br J Pharmacol 162:1–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ibrahim L, Diazgranados N, Luckenbaugh DA, Machado-Vieira R, Baumann J, Mallinger AG et al (2011) Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression. Prog Neuropsychopharmacol Biol Psychiatry 35:1155–1159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Duman RS (2014) Neurobiology of stress, depression, and rapid acting antidepressants: remodeling of synaptic connections. Depress Anxiety 31:291–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Zhang Y, Xu Z, Zhang S, Desrosiers A, Schottenfeld RS, Chawarski MC (2014) Profiles of psychiatric symptoms among amphetamine type stimulant and ketamine using inpatients in Wuhan. China J Psychiatric Res 53:99–102

    Article  Google Scholar 

  80. Moghaddam B, Adams B, Verma A, Daly D (1997) 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. J Neuroscience 17:2921–2927

    Article  CAS  Google Scholar 

  81. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M et al (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Jourdi H, Hsu YT, Zhou M, Qin Q, Bi X, Baudry M (2009) Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J Neurosci 29:8688–8697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Beurel E, Song L, Jope RS (2011) Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice. Mol Psychiatry 16:1068–1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Duman RS (2012) Aghajanian GK.Synaptic dysfunction in depression: potential therapeutic targets. Science 338:68–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kraus C, Wasserman D, Henter ID, Acevedo-Diaz E, Kadriu B, Zarate CA Jr (2019) The influence of ketamine on drug discovery in depression. Drug Discov Today. https://doi.org/10.1016/j.drudis.2019.07.007

    Article  PubMed  PubMed Central  Google Scholar 

  86. Carlén M, Meletis K, Siegle J et al (2012) A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior. Mol Psychiatry 17:537–548. https://doi.org/10.1038/mp.2011.31

    Article  CAS  PubMed  Google Scholar 

  87. Pham TH, Gardier AM (2019) Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies. Pharmacol Ther 199:58–90

    Article  CAS  PubMed  Google Scholar 

  88. Janko S, Laslo P, Miljana O, Dijana LP, Dragan OI (2014) Antidepressant effects of an inverse agonist selective for α5 gaba-a receptors in the rat forced swim test. Acta Vet-Beogr 64(1):52–60

    Article  Google Scholar 

  89. Sanchez C, Ke A, Artigas F (2015) Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol Ther 145:43–57

    Article  CAS  PubMed  Google Scholar 

  90. Chen G, Lee R, Hojer AM, Buchbjerg JK, Serenko M, Zhao Z (2013) Pharmacokinetic drug interactions involving vortioxetine (Lu AA21004), a multimodal antidepressant. Clin Drug Investig 33(10):727–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Mørk A, Pehrson A, Brennum LT (2012) Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther 340(3):666–675

    Article  PubMed  CAS  Google Scholar 

  92. Pehrson AL, Cremers T, Bétry C, van der Hart MG, Jørgensen L, Madsen M, Haddjeri N, Ebert B, Sanchez C. (2013) Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters--a rat microdialysis and electrophysiology study. Eur Neuropsychopharmacol. Feb;23(2):133–45. https://doi.org/10.1016/j.euroneuro.2012.04.006.

  93. Haddjeri N, Etievant A, Pehrson A, Sanchez C, Betry C (2012) Effects of the multimodal antidepressant Lu AA21004 on rat synaptic and cellular hippocampal plasticity and memory recognition. Eur Neuropsychopharmacol 22:S303

    Article  Google Scholar 

  94. Guilloux JP, Mendez-David I, Pehrson A, Guiard BP, Repérant C, Orvoën S, Gardier AM, Hen R, Ebert B, Miller S, Sanchez C, David DJ (2013) Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice. Neuropharmacology 73:147–159. https://doi.org/10.1016/j.neuropharm.2013.05.014

    Article  CAS  PubMed  Google Scholar 

  95. Connolly KR, Thase ME (2016) Vortioxetine: a new treatment for major depressive disorder. Expert Opin Pharmacother 17(3):421–431. https://doi.org/10.1517/14656566.2016.1133588

    Article  CAS  PubMed  Google Scholar 

  96. Hanoun N, Mocaër E, Boyer PA, Hamon M, Lanfumey L (2004) Differential effects of the novel antidepressant agomelatine (S 20098) versus fluoxetine on 5-HT1A receptors in the rat brain. Neuropharmacology 47(4):515–526. https://doi.org/10.1016/j.neuropharm.2004.06.003

    Article  CAS  PubMed  Google Scholar 

  97. Pineyro G, Blier P (1999) Autoregulation of serotonin neurons: role in antidepressant drug action. Pharmacol Rev 51:533–591

    CAS  PubMed  Google Scholar 

  98. Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, Rivet JM, Cussac D (2003) The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 306(3):954–964. https://doi.org/10.1124/jpet.103.051797

    Article  CAS  PubMed  Google Scholar 

  99. Millan MJ, Brocco M, Gobert A, Dekeyne A (2005) Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology 177(4):448–458. https://doi.org/10.1007/s00213-004-1962-z

    Article  CAS  PubMed  Google Scholar 

  100. Bogaards JJ, Hissink EM, Briggs M, Weaver R, Jochemsen R, Jackson P, Bertrand M, van Bladeren PJ (2000) Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling. Eur J Pharm Sci 12(2):117–124. https://doi.org/10.1016/s0928-0987(00)00146-9

    Article  CAS  PubMed  Google Scholar 

  101. Barden N, Shink E, Labbé M, Vacher R, Rochford J, Mocaër E (2005) Antidepressant action of agomelatine (S 20098) in a transgenic mouse model. Prog Neuropsychopharmacol Biol Psychiatry 29(6):908–916. https://doi.org/10.1016/j.pnpbp.2005.04.032

    Article  CAS  PubMed  Google Scholar 

  102. Bourin M, Mocaer E, Porsolt R (2004) Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors. J Psychiatry Neurosci 29:126–133

    PubMed  PubMed Central  Google Scholar 

  103. Bertaina-Anglade V, la Rochelle CD, Boyer PA, Mocaër E (2006) Antidepressant-like effects of agomelatine (S 20098) in the learned helplessness model. Behav Pharmacol 17(8):703–713. https://doi.org/10.1097/FBP.0b013e3280116e5c (PMID: 17110796)

    Article  CAS  PubMed  Google Scholar 

  104. Loo H, Hale A, D’haenen H (2002) Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT (2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study. Int Clin Psychopharmacol 17:239–247

    Article  CAS  PubMed  Google Scholar 

  105. Kennedy SH, Emsley R (2006) Placebo-controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharmacol 16:93–100

    Article  CAS  PubMed  Google Scholar 

  106. Audinot V, Mailliet F, Lahaye-Brasseur C, Bonnaud A, Le Gall A, Amossé C, Dromaint S, Rodriguez M, Nagel N, Galizzi JP, Malpaux B, Guillaumet G, Lesieur D, Lefoulon F, Renard P, Delagrange P, Boutin JA (2003) New selective ligands of human cloned melatonin MT1 and MT2 receptors. Naunyn Schmiedebergs Arch Pharmacol 367(6):553–561. https://doi.org/10.1007/s00210-003-0751-2

    Article  CAS  PubMed  Google Scholar 

  107. den Boer JA, Bosker FJ, Meesters Y (2006) Clinical efficacy of agomelatine in depression: the evidence. Int Clin Psychopharmacol 21(Suppl 1):S21–S24. https://doi.org/10.1097/01.yic.0000195661.37267.86

    Article  Google Scholar 

  108. Licht CL, Marcussen AB, Wegener G, Overstreet DH, Aznar S, Knudsen GM (2009) The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration. J Neurochem 109:1363–1374

    Article  CAS  PubMed  Google Scholar 

  109. Frazer. A., Pharmacology of antidepressants. (1997) J Clin Psychopharmacol. 17 Suppl, 1:2S-18S.

  110. Brunton, L, Chabner, B, Goodman KB, Gilman's. The pharmacological basis of therapeutics (2010) New York: McGraw-Hill Professional, , ISBN 978–0–07–162442–8.

  111. Aleksandrova LR, Phillips AG, Wang YT (2017) Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism. J Psychiatry Neurosci 42:4

    Article  Google Scholar 

  112. Chavez-Castillo M, Nuñez V, Nava M, Ortega A, Rojas M, Bermudez V, Rojas-Quintero J. (2019) Depression as a neuroendocrine disorder: emerging neuropsychopharmacological approaches beyond monoamines, Advances in pharmacological sciences. (20).

  113. Sriharsha K (2015) Cross-talk and regulation between glutamate and GABA receptors. Front Cell Neurosci 9:135

    Google Scholar 

  114. Witkin JM (2020) mGlu2/3 receptor antagonism: a mechanism to induce rapid antidepressant effects without ketamine-associated side-effects. Pharmacol Biochem Behav 190:172854

    Article  CAS  PubMed  Google Scholar 

  115. Hazell GG, Hindmarch CC, Pope GR, Roper JA, Lightman SL, Murphy D, O’Carroll AM, Lolait SJ (2012) G protein-coupled receptors in the hypothalamic paravencular and supraoptic nuclei–serpentine gateways to neuroendocrine homeostasis. Front Neuroendocrinol 33(1):45–66. https://doi.org/10.1016/j.yfrne.2011.07.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Jeon SW, Kim YK (2016) Molecular neurobiology and promising new treatment in depression. Int J Mol Sci 17:381. https://doi.org/10.3390/ijms17030381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Richelson E (1990) Antidepressants and brain neurochemistry. Mayo Clin Proc 65:1227–1236

    Article  CAS  PubMed  Google Scholar 

  118. Vahid-Ansari F, Zhang M, Amin Zahrai APR. (2019) Overcoming resistance to selective serotonin reuptake inhibitors: targeting serotonin, serotonin-1A receptors and adult neuroplasticity. Front. Neuroscihttps://doi.org/10.3389/fnins.2019.00404

  119. Wolfe BB, Harden TK, Sporn JR, Molinoff PB (1978) Presynaptic modulation of beta adrenergic receptors in rat cerebral cortex after treatment with antidepressants. J Pharmacol Exp Ther 207:446–457

    CAS  PubMed  Google Scholar 

  120. Janowsky A, Steranka LR, Gillespie DD, Sulser F (1982) Role of neuronal signal input in the down-regulation of central noradrenergic receptor function by antidepressant drugs. J Neurochem 39:290–292

    Article  CAS  PubMed  Google Scholar 

  121. Heninger GR, Charney DS, Price LH (1988) Adrenergic receptor sensitivity in depression: the plasma MHPG, behavioral, and cardiovascular responses to yohimbine. Arch Gen Psychiatry 45:718–726

    Article  CAS  PubMed  Google Scholar 

  122. Pollack MH, Rosenbaum JF, Cassem NH (1985) Propran 0101 and depression revisited: three cases and a review. J NervMent Dis 173:118–119

    Article  CAS  Google Scholar 

  123. Tommonaro G, García-Font N, Vitale RM, Pejin B, Iodice C, Cañadas S, Oset-Gasque MJ (2016) Avarol derivatives as competitive AChE inhibitors. Eur J Med Chem 122:326–338. https://doi.org/10.1016/j.ejmech.2016.06.036

    Article  CAS  PubMed  Google Scholar 

  124. Pejin B, Iodice C, Tommonaro G, De Rosa S (2008) Synthesis and biological activities of thio-avarol derivatives. J Nat Prod 71(11):1850–1853

    Article  CAS  PubMed  Google Scholar 

  125. Contractor A, Swanson GT, Sailer A, O’Gorman S, Heinemann SF (2000) Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus. J Neurosci 20:8269–8278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Lauri SE, Bortolotto ZA, Bleakman D, Ornstein PL, Lodge D, Isaac JT, Collingridge GL (2001) A critical role of a facilitatory presynaptic kainate receptor in mossy fiber LTP. Neuron 32(4):697–709. https://doi.org/10.1016/s0896-6273(01)00511-6

    Article  CAS  PubMed  Google Scholar 

  127. Feng L, Molnár P, Nadler JV (2003) Short-term frequency-dependent plasticity at recurrent mossy fiber synapses of the epileptic brain. J Neurosci 23:5381–5390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Kobayashi K, Ikeda Y, Asada M, Inagaki H, Kawada T, Suzuki H (2013) Corticosterone facilitates fluoxetine-induced neuronal plasticity in the hippocampus. PLoS ONE 8:e63662. https://doi.org/10.1371/journal.pone.0063662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T, Suzuki H (2010) Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proc Natl Acad Sci U S A 107(18):8434–8439. https://doi.org/10.1073/pnas.0912690107

    Article  PubMed  PubMed Central  Google Scholar 

  130. Ohira K, Takeuchi R, Shoji H, Miyakawa T (2013) Fluoxetine induced cortical adult neurogenesis. Neuropsychopharmacology 38(6):909–920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Takao K, Kobayashi K, Hagihara H, Ohira K, Shoji H, Hattori S, Koshimizu H, Umemori J, Toyama K, Nakamura HK, Kuroiwa M, Maeda J, Atsuzawa K, Esaki K, Yamaguchi S, Furuya S, Takagi T, Walton NM, Hayashi N, Suzuki H, Higuchi M, Usuda N, Suhara T, Nishi A, Matsumoto M, Ishii S, Miyakawa T (2013) Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia. Neuropsychopharmacology 38(8):1409–1425. https://doi.org/10.1038/npp.2013.38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Klempin F, Babu H, De Pietri TD, Alarcon E, Fabel K, Kempermann G (2010) Oppositional effects of serotonin receptors 5-HT1a, 2, and 2c in the regulation of adult hippocampal neurogenesis. Front Mol Neurosci 3:14. https://doi.org/10.3389/fnmol.2010.00014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Imoto Y, Segi-Nishida E, Suzuki H, Kobayashi K (2017) Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment. Mol Brain 10:8. https://doi.org/10.1186/s13041-017-0288-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Imoto Y, Kira T, Sukeno M, Nishitani N, Nagayasu K, Nakagawa T, Shuji Kaneko S, Kobayashi K, Segi-Nishida E (2015) Role of the 5-HT4 receptor in chronic fluoxetine treatment-induced neurogenic activity and granule cell dematuration in the dentate gyrus. Mol Brain 8:29. https://doi.org/10.1186/s13041-015-0120-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Samuels BA, Anacker C, Hu A, Levinstein MR, Pickenhagen A, Tsetsenis T, Madroñal N, Donaldson ZR, Drew LJ, Dranovsky A, Gross CT, Tanaka KF, Hen R (2015) 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response. Nat Neurosci 18(11):1606–1616. https://doi.org/10.1038/nn.4116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Rojas PS, Fiedler JL (2016) What do we really know about 5-HT1A receptor signaling in neuronal cells? Front Cell Neurosci 10:272. https://doi.org/10.3389/fncel.2016.00272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Davidson RJ, Irwin W, Anderle MJ, Kalin NH (2003) The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatr 160:64–75

    Article  PubMed  Google Scholar 

  138. Fu CH, Williams SC, Cleare AJ, Brammer MJ, Walsh ND, Kim J, Andrew CM, Pich EM, Williams PM, Reed LJ, Mitterschiffthaler MT, Suckling J, Bullmore ET (2004) Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Arch Gen Psychiatry 61(9):877–889. https://doi.org/10.1001/archpsyc.61.9.877 (PMID: 15351766)

    Article  PubMed  Google Scholar 

  139. Victor TA, Furey ML, Fromm SJ, Ohman A, Drevets WC (2010) Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder. Arch Gen Psychiatry 67:1128–1138

    Article  PubMed  PubMed Central  Google Scholar 

  140. Delaveau P, Jabourian M, Lemogne C, Guionnet S, Bergouignan L, Fossati P (2011) Brain effects of antidepressants in major depression: a meta–analysis of emotional processing studies. J Affect Disord 130:66–74

    Article  CAS  PubMed  Google Scholar 

  141. Boldrini M, Santiago AN, Hen R, Dwork AJ, Rosoklija GB, Tamir H, Arango V, John MJ (2013) Hippocampal granule neuron number and dentate gyrus volume in antidepressant-treated and untreated major depression. Neuropsychopharmacology 38(6):1068–1077. https://doi.org/10.1038/npp.2013.5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Tanaka KF, Samuels BA, Hen R (2012) Serotonin receptor expression along the dorsal-ventral axis of mouse hippocampus. Philos Trans R Soc Lond B Biol Sci 367(1601):2395–2401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Imoto Y, Kira T, Sukeno M, Nishitani N, Nagayasu K, Nakagawa T, Kaneko S, Kobayashi K, Segi-Nishida E (2015) Role of the 5-HT4 receptor in chronic fluoxetine treatment-induced neurogenic activity and granule cell dematuration in the dentate gyrus. Mol Brain 8:29. https://doi.org/10.1186/s13041-015-0120-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Amigo J, Díaz A, Pilar-Cuellar F, Vidal R, Martín A, Compan V, Pazos A, Castro E (2016) The absence of 5-HT4 receptors modulates depression- and anxiety-like responses and influences the response of fluoxetine in olfactory bulbectomised mice: adaptive changes in hippocampal neuroplasticity markers and 5-HT1A autoreceptor. Neuropharmacology 111:47–58

    Article  CAS  PubMed  Google Scholar 

  145. Hodes GE, Hill-Smith TE, Lucki I. (2010) Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice. Neurosci Lett. 484(1):12–6. https://doi.org/10.1016/j.neulet.2010.07.084. Epub 2010 Aug 6. PMID: 20692322; PMCID: PMC4623584.

  146. Neto FL, Borges G, Torres-Sanchez S, Mico JA, Esther BE (2011) Neurotrophins role in depression neurobiology: a review of basic and clinical evidence. CurrNeuropharmacol 9(4):530–552. https://doi.org/10.2174/157015911798376262

    Article  CAS  Google Scholar 

  147. Fossati P, Radtchenko A, Boyer P (2004) Neuroplasticity: from MRI to depressive symptoms. Eur Neuropsychopharmacol 14(Suppl 5):S503–S510

    Article  CAS  PubMed  Google Scholar 

  148. Sheline YI, Disabato BM, Hranilovich J, Morris C, D’Angelo G, Pieper C, Toffanin T, Taylor WD, MacFall JR, Wilkins C, Barch DM, Welsh-Bohmer KA, Steffens DC, Krishnan RR, Doraiswamy PM (2012) Treatment course with antidepressant therapy in late-life depression. Am J Psychiatry 169(11):1185–1193. https://doi.org/10.1176/appi.ajp.2012.12010122

    Article  PubMed  PubMed Central  Google Scholar 

  149. Chen CH, Ridler K, Suckling J, Williams S, Fu CH, Merlo-Pich E, Bullmore E (2007) Brain imaging correlates of depressive symptom severity and predictors of symptom improvement after antidepressant treatment. Biol Psychiatry 62(5):407–414. https://doi.org/10.1016/j.biopsych.2006.09.018

    Article  CAS  PubMed  Google Scholar 

  150. Yucel K, McKinnon M, Chahal R, Taylor V, Macdonald K, Joffe R, MacQueen G (2009) Increased subgenual prefrontal cortex size in remitted patients with major depressive disorder. Psychiatry Res 173(1):71–76. https://doi.org/10.1016/j.pscychresns.2008.07.013

    Article  PubMed  Google Scholar 

  151. Costafreda SG, Chu C, Ashburner J, Fu CH (2009) Prognostic and diagnostic potential of the structural neuroanatomy of depression. PLoS ONE 4(7):e6353. https://doi.org/10.1371/journal.pone.0006353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Kong L, Wu F, Tang Y, Ren L, Kong D, Liu Y, Xu K, Wang F (2014) Frontal-subcortical volumetric deficits in single episode, medication-naive depressed patients and the effects of 8 weeks fluoxetine treatment: a VBM-DARTEL study. PLoS ONE 9(1):e79055. https://doi.org/10.1371/journal.pone.0079055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Smith R, Chen K, Baxter L, Fort C, Lane RD (2013) Antidepressant effects of sertraline associated with volume increases in dorsolateral prefrontal cortex. J Affect Disord 146(3):414–419. https://doi.org/10.1016/j.jad.2012.07.029

    Article  CAS  PubMed  Google Scholar 

  154. Lavretsky H, Roybal DJ, Ballmaier M, Toga AW, Kumar A (2005) Antidepressant exposure may protect against decrement in frontal gray matter volumes in geriatric depression. J Clin Psychiatry 66(8):964–967. https://doi.org/10.4088/JCP.v66n0801

    Article  PubMed  Google Scholar 

  155. Caccia S (1998) Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications. Clin Pharmacokinet 34(4):281–302. https://doi.org/10.2165/00003088-199834040-00002

    Article  CAS  PubMed  Google Scholar 

  156. Pacher P, Kohegyi E, Kecskemeti V, Furst S (2001) Current trends in the development of new antidepressants. Curr Med Chem 8(2):89–100. https://doi.org/10.2174/0929867013373796

    Article  CAS  PubMed  Google Scholar 

  157. Christopher M, Lysaker PH (2007) The “chemical imbalance” explanation for depression: origins, lay endorsement, and clinical implications. Prof Psychol Res Pract 38(4):411–442

    Article  Google Scholar 

  158. Taylor C, Fricker AD, Devi LA, Gomes I (2005) Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways. Cell signal 17(5):549–557. https://doi.org/10.1016/j.cellsig.2004.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Peng GJ, Tian JS, Gao XX, Zhou YZ, Qin XM (2015) Research on the pathological mechanism and drug treatment mechanism of depression. CurrNeuropharmacol 13(4):514–523. https://doi.org/10.2174/1570159X1304150831120428

    Article  CAS  Google Scholar 

  160. Segi-Nishida E (2017) The effect of serotonin-targeting antidepressants on neurogenesis and neuronal maturation of the hippocampus mediated via 5-HT1A and 5-HT4 receptors. Front Cell Neurosci 11:142. https://doi.org/10.3389/fncel.2017.00142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Carr GV, Lucki I (2011) The role of serotonin receptor subtypes in treating depression: a review of animal studies. Psychopharmacology 213(2–3):265–287. https://doi.org/10.1007/s00213-010-2097-z

    Article  CAS  PubMed  Google Scholar 

  162. Cornelisse LN, Van der Harst JE, Lodder JC, Baarendse PJ, Timmerman AJ, Mansvelder HD et al (2007) Reduced 5-HT1A and GABAB receptor function in dorsal raphe neurons upon chronic fluoxetine treatment of socially stressed rats. J Neurophysiol 98:196–204

    Article  CAS  PubMed  Google Scholar 

  163. Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G et al (2008) Cellular mechanisms underlying the antidepressant effects of ketamine: role of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiat 63:349–352

    Article  CAS  PubMed  Google Scholar 

  164. Yamasaki N, Maekawa M, Kobayashi K, Kajii Y, Maeda J, Soma M, Takao K, Tanda K, Ohira K, Toyama K, Kanzaki K, Fukunaga K, Sudo Y, Ichinose H, Ikeda M, Iwata N, Ozaki N, Suzuki H, Higuchi M, Suhara T, Yuasa S, Miyakawa T (2008) Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders. Mol Brain 1:6. https://doi.org/10.1186/1756-6606-1-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Cartwright C, Gibson K, Read J, Cowan O, Dehar T (2016) Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient prefer adherence 10:1401–1407. https://doi.org/10.2147/PPA.S110632

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank UGC-SAP and DST-FIST for providing facilities to conduct research. The authors also thank the Deanship of Scientific Research and RSSU at King Saud University for their technical support.

Funding

Khushboo is thankful to UGC-New Delhi for financial support in the form of a fellowship. BS is grateful to UPCST-Lucknow for financial support in the form of a Research Grant. M.d.L.P. acknowledges the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MCTES and when appropriate co-financed by FEDER under the PT2020 partnership agreement.

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Allahabad, Allahabad, 211002, India

    Khushboo & Bechan Sharma

  2. Department of Biochemistry, King Saud University, Riyadh, Saudi Arabia

    Nikhat J. Siddiqi

  3. Department of Medical Sciences, CICECO-Aveiro Institute of Materials &, University of Aveiro, 3810-193, Aveiro, Portugal

    Maria de Lourdes Pereira

Authors
  1. Khushboo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikhat J. Siddiqi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria de Lourdes Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bechan Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Khushboo searched the concerned information on the topic from various sources, organized the information systematically, made proper analysis, and presented first draft of the manuscript. BS conceived the idea, decided different aspects of the topic, and added the relevant contents in the manuscript. NJS and MLP critically reviewed the manuscript and provided their valuable inputs.

Corresponding author

Correspondence to Bechan Sharma.

Ethics declarations

Ethics approval

Not applicable.

Consent to Participate

All the authors have participated in preparation of the manuscript.

Consent for Publication

All the authors extend their consents for publication of this manuscript.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khushboo, Siddiqi, N.J., de Lourdes Pereira, M. et al. Neuroanatomical, Biochemical, and Functional Modifications in Brain Induced by Treatment with Antidepressants. Mol Neurobiol 59, 3564–3584 (2022). https://doi.org/10.1007/s12035-022-02780-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-022-02780-z

Keywords

Search

Navigation