692
Views
0
CrossRef citations to date
0
Altmetric
Original Research

Potentiation of antidepressant effects: NPY1R agonist and ketamine synergy enhances TrkB signaling and neurogenesis in the ventral hippocampus

, , , , , & ORCID Icon show all
Pages 309-322 | Received 04 Mar 2024, Accepted 05 Apr 2024, Published online: 18 Apr 2024

References

  • Catala-Lopez F, Genova-Maleras R, Vieta E, et al. The increasing burden of mental and neurological disorders. Eur Neuropsychopharmacol. 2013 Nov;23(11):1337–1339.
  • McEwen BS, Bowles NP, Gray JD, et al. Mechanisms of stress in the brain. Nat Neurosci. 2015 Oct;18(10):1353–1363.
  • Schramm E, Klein DN, Elsaesser M, et al. Review of dysthymia and persistent depressive disorder: history, correlates, and clinical implications. Lancet Psychiatry. 2020 Sep;7(9):801–812.
  • Kessler RC, Petukhova M, Sampson NA, et al. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012 Sep;21(3):169–184.
  • Karch DL, Logan J, McDaniel D, et al. Surveillance for violent deaths–national violent death reporting system, 16 states, 2009. MMWR Surveill Summ. 2012 Sep 14;61(6):1–43.
  • Aleman A, Denys D. Mental health: a road map for suicide research and prevention. Nature. 2014 May 22;509(7501):421–423. doi: 10.1038/509421a
  • World Health O. Front Matter. Depression and other common mental disorders. World Health Org. 2017. p. 2–2.
  • Fitzmaurice C, Akinyemiju TF, Barber RM, et al. Global Burden of Disease Cancer C. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: a systematic analysis for the global burden of disease study. JAMA Oncol. 2018 Nov 1: 4(11):1553–1568.
  • Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA. 2004 Jul 21;292(3):338–343. doi: 10.1001/jama.292.3.338
  • Morilak DA, Frazer A. Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders. Int J Neuropsychopharmacol. 2004 Jun;7(2):193–218. doi: 10.1017/S1461145704004080
  • Kudlow PA, Cha DS, McIntyre RS. Predicting treatment response in major depressive disorder: the impact of early symptomatic improvement. Can J Psychiatry. 2012 Dec;57(12):782–788. doi: 10.1177/070674371205701211
  • Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006 Jan;163(1):28–40.
  • Fagiolini A, Kupfer DJ. Is treatment-resistant depression a unique subtype of depression? Biol Psychiatry. 2003 Apr 15;53(8):640–648.
  • Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351–354. doi: 10.1016/S0006-3223(99)00230-9
  • Zarate CA Jr., Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856–864.
  • Krystal JH, Sanacora G, Duman RS. Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. Biol Psychiatry. 2013 Jun 15;73(12):1133–1141. doi: 10.1016/j.biopsych.2013.03.026
  • Liao Y, Tang YL, Hao W. Ketamine and international regulations. Am J Drug Alcohol Abuse. 2017 Sep;43(5):495–504. doi: 10.1080/00952990.2016.1278449
  • Duman RS. Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide. F1000Res. 2018;7:659. doi: 10.12688/f1000research.14344.1
  • Targum SD, Daly E, Fedgchin M, et al. Comparability of blinded remote and site-based assessments of response to adjunctive esketamine or placebo nasal spray in patients with treatment resistant depression. J Psychiatr Res. 2019 Apr;111:68–73. doi: 10.1016/j.jpsychires.2019.01.017
  • Zimmermann KS, Richardson R, Baker KD. Esketamine as a treatment for paediatric depression: questions of safety and efficacy. Lancet Psychiatry. 2020 Oct;7(10):827–829. doi: 10.1016/S2215-0366(19)30521-8
  • Turner EH. Esketamine for treatment-resistant depression: seven concerns about efficacy and FDA approval. Lancet Psychiatry. 2019 Dec;6(12):977–979. doi: 10.1016/S2215-0366(19)30394-3
  • Kaur U, Pathak BK, Singh A, et al. Esketamine: a glimmer of hope in treatment-resistant depression. Eur Arch Psychiatry Clin Neurosci. 2021 Apr;271(3):417–429.
  • Zanos P, Moaddel R, Morris PJ, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016 May 26;533(7604):481–486. doi: 10.1038/nature17998
  • Fukumoto K, Toki H, Iijima M, et al. Antidepressant potential of (r)-ketamine in rodent models: comparison with (S)-Ketamine. J Pharmacol Exp Ther. 2017 Apr;361(1):9–16.
  • Mahar I, Bambico FR, Mechawar N, et al. Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neurosci Biobehav Rev. 2014 Jan;38:173–192. doi: 10.1016/j.neubiorev.2013.11.009
  • Eliwa H, Belzung C, Surget A. Adult hippocampal neurogenesis: Is it the alpha and omega of antidepressant action? Biochem Pharmacol. 2017 Oct 1;141:86–99. doi: 10.1016/j.bcp.2017.08.005
  • Haroon E, Miller AH, Sanacora G. Inflammation, glutamate, and glia: a trio of trouble in mood disorders. Neuropsychopharmacology. 2017 Jan;42(1):193–215. doi: 10.1038/npp.2016.199
  • Thorsell A, Mathe AA. Neuropeptide Y in alcohol addiction and affective disorders. Front Endocrinol. 2017;8:178. doi: 10.3389/fendo.2017.00178
  • Castren E, Monteggia LM. Brain-derived neurotrophic factor signaling in depression and antidepressant action. Biol Psychiatry. 2021 Jul 15;90(2):128–136. doi: 10.1016/j.biopsych.2021.05.008
  • Pothula S, Kato T, Liu RJ, et al. Cell-type specific modulation of NMDA receptors triggers antidepressant actions. Mol Psychiatry. 2021 Sep;26(9):5097–5111.
  • Gerhard DM, Pothula S, Liu RJ, et al. GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions. J Clin Invest. 2020 Mar 2;130(3):1336–1349. doi: 10.1172/JCI130808
  • Autry AE, Adachi M, Nosyreva E, et al. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature. 2011 Jun 15;475(7354):91–95. doi: 10.1038/nature10130
  • Kavalali ET, Monteggia LM. Targeting homeostatic synaptic plasticity for treatment of mood disorders. Neuron. 2020 Jun 3;106(5):715–726. doi: 10.1016/j.neuron.2020.05.015
  • Casarotto PC, Girych M, Fred SM, et al. Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell. 2021 Mar 4;184(5):1299–1313 e19. doi: 10.1016/j.cell.2021.01.034
  • Kask A, Harro J, von Horsten S, et al. The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y. Neurosci Biobehav Rev. 2002 May;26(3):259–283.
  • Kormos V, Gaszner B. Role of neuropeptides in anxiety, stress, and depression: from animals to humans. Neuropeptides. 2013 Dec;47(6):401–419. doi: 10.1016/j.npep.2013.10.014
  • Zaben MJ, Gray WP. Neuropeptides and hippocampal neurogenesis. Neuropeptides. 2013 Dec;47(6):431–438. doi: 10.1016/j.npep.2013.10.002
  • Reichmann F, Holzer P. Neuropeptide Y: a stressful review. Neuropeptides. 2016 Feb;55:99–109. doi: 10.1016/j.npep.2015.09.008
  • Jimenez-Vasquez PA, Diaz-Cabiale Z, Caberlotto L, et al. Electroconvulsive stimuli selectively affect behavior and neuropeptide Y (NPY) and NPY Y(1) receptor gene expressions in hippocampus and hypothalamus of flinders sensitive line rat model of depression. Eur Neuropsychopharmacol. 2007 Mar;17(4):298–308.
  • Redrobe JP, Dumont Y, Fournier A, et al. The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY-induced antidepressant-like activity in the mouse forced swimming test. Neuropsychopharmacology. 2002 May;26(5):615–624.
  • Goyal SN, Upadhya MA, Kokare DM, et al. Neuropeptide Y modulates the antidepressant activity of imipramine in olfactory bulbectomized rats: involvement of NPY Y1 receptors. Brain Res. 2009 Apr 17;1266:45–53. doi: 10.1016/j.brainres.2009.02.033
  • Sharma A, Ren X, Zhang H, et al. Effect of depression and suicidal behavior on neuropeptide Y (NPY) and its receptors in the adult human brain: a postmortem study. Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jan 10;112:110428. doi: 10.1016/j.pnpbp.2021.110428
  • Corvino V, Marchese E, Podda MV, et al. The neurogenic effects of exogenous neuropeptide Y: early molecular events and long-lasting effects in the hippocampus of trimethyltin-treated rats. PLOS ONE. 2014;9(2):e88294. doi: 10.1371/journal.pone.0088294
  • Cohen H, Liu T, Kozlovsky N, et al. The neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder. Neuropsychopharmacology. 2012 Jan;37(2):350–363.
  • Cohen H, Vainer E, Zeev K, et al. Neuropeptide S in the basolateral amygdala mediates an adaptive behavioral stress response in a rat model of posttraumatic stress disorder by increasing the expression of BDNF and the neuropeptide YY1 receptor. Eur Neuropsychopharmacol. 2018 Jan;28(1):159–170.
  • Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977 Apr 21;266(5604):730–732. doi: 10.1038/266730a0
  • Planchez B, Surget A, Belzung C. Animal models of major depression: drawbacks and challenges. J Neural Transm (Vienna). 2019 Nov;126(11):1383–1408. doi: 10.1007/s00702-019-02084-y
  • Yankelevitch-Yahav R, Franko M, Huly A, et al. The forced swim test as a model of depressive-like behavior. J Vis Exp. 2015 Mar 2;(97). doi: 10.3791/52587.
  • Serova L, Mulhall H, Sabban E. NPY1 receptor agonist modulates development of depressive-like behavior and gene expression in hypothalamus in SPS rodent PTSD model. Front Neurosci. 2017;11:203. doi: 10.3389/fnins.2017.00203
  • Borroto-Escuela DO, Fores R, Pita M, et al. Intranasal delivery of galanin 2 and neuropeptide Y1 agonists enhanced spatial memory performance and neuronal precursor cells proliferation in the dorsal hippocampus in rats. Front Pharmacol. 2022;13:820210. doi: 10.3389/fphar.2022.820210
  • Ribeiro ACR, Zhu J, Kronfol MM, et al. Molecular mechanisms for the antidepressant-like effects of a low-dose ketamine treatment in a DFP-based rat model for gulf war illness. Neurotoxicology. 2020 Sep;80:52–59. doi: 10.1016/j.neuro.2020.06.011
  • Koike H, Chaki S. Requirement of AMPA receptor stimulation for the sustained antidepressant activity of ketamine and LY341495 during the forced swim test in rats. Behav Brain Res. 2014 Sep 1;271:111–115. doi: 10.1016/j.bbr.2014.05.065
  • Borroto-Escuela DO, Pita-Rodriguez M, Fores-Pons R, et al. Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus. J Cell Physiol. 2021 May;236(5):3565–3578.
  • Narváez M, Crespo-Ramírez M, Fores-Pons R, et al. Study of GPCR homo- and heteroreceptor complexes in specific neuronal cell populations using the in situ proximity ligation assay. In: Lujan R Ciruela F, editors. Receptor and ion channel detection in the brain. New York (NY): Springer US; 2021. p. 117–134.
  • Narvaez M, Andrade-Talavera Y, Valladolid-Acebes I, et al. Existence of FGFR1-5-HT1AR heteroreceptor complexes in hippocampal astrocytes. Putative link to 5-HT and FGF2 modulation of hippocampal gamma oscillations. Neuropharmacology. 2020 Jun 15;170:108070. doi: 10.1016/j.neuropharm.2020.108070
  • Diaz-Sanchez E, Lopez-Salas A, Mirchandani-Duque M, et al. Decreased medial prefrontal cortex activity related to impaired novel object preference task performance following GALR2 and Y1R agonists intranasal infusion. Biomed Pharmacother. 2023 May;161:114433. doi: 10.1016/j.biopha.2023.114433
  • Abrial E, Betourne A, Etievant A, et al. Protein kinase C inhibition rescues manic-like behaviors and hippocampal cell proliferation deficits in the sleep deprivation model of mania. Int J Neuropsychopharmacol. 2014 Oct 31;18(2). doi: 10.1093/ijnp/pyu031
  • Pilar-Cuellar F, Vidal R, Pazos A. Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, beta-catenin and antidepressant-like effects. Br J Pharmacol. 2012 Feb;165(4b):1046–1057. doi: 10.1111/j.1476-5381.2011.01516.x
  • Paxinos G, Watson C. The rat brain in stereotaxic coordinates: hard cover edition. AE Amsterdam, The netherlands: Elsevier; 2006.
  • Narvaez M, Borroto-Escuela DO, Santin L, et al. A novel integrative mechanism in anxiolytic behavior induced by galanin 2/Neuropeptide Y Y1 receptor interactions on medial paracapsular intercalated amygdala in rats. Front Cell Neurosci. 2018;12:119. doi: 10.3389/fncel.2018.00119
  • Mirchandani-Duque M, Barbancho MA, Lopez-Salas A, et al. Galanin and neuropeptide Y interaction enhances proliferation of granule precursor cells and expression of neuroprotective factors in the rat hippocampus with consequent augmented spatial memory. Biomedicines. 2022 Jun 1;10(6):1297. doi: 10.3390/biomedicines10061297
  • Narvaez M, Millon C, Borroto-Escuela D, et al. Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the amygdala lead to increased anxiolytic actions. Brain Struct Funct. 2015 Jul;220(4):2289–2301.
  • Narvaez M, Borroto-Escuela DO, Millon C, et al. Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the dentate gyrus are related with antidepressant-like effects. Brain Struct Funct. 2016 Nov;221(8):4129–4139.
  • Cohen H, Zohar J, Kaplan Z, et al. Adjunctive treatment with brexpiprazole and escitalopram reduces behavioral stress responses and increase hypothalamic NPY immunoreactivity in a rat model of PTSD-like symptoms. Eur Neuropsychopharmacol. 2018 Jan;28(1):63–74.
  • Li N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010 Aug 20;329(5994):959–964. doi: 10.1126/science.1190287
  • Polis AJ, Fitzgerald PJ, Hale PJ, et al. Rodent ketamine depression-related research: finding patterns in a literature of variability. Behav Brain Res. 2019 Dec 30;376:112153. doi: 10.1016/j.bbr.2019.112153
  • Detke MJ, Rickels M, Lucki I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacol (Berl). 1995 Sep;121(1):66–72. doi: 10.1007/BF02245592
  • Rafalo-Ulinska A, Branski P, Palucha-Poniewiera A. Combined administration of (R)-ketamine and the mGlu2/3 receptor antagonist LY341495 induces rapid and sustained effects in the CUMS model of depression via a TrkB/BDNF-dependent mechanism. Pharmaceuticals (Basel). 2022 Jan 21;15(2):125. doi: 10.3390/ph15020125
  • Liu RJ, Fuchikami M, Dwyer JM, et al. GSK-3 inhibition potentiates the synaptogenic and antidepressant-like effects of subthreshold doses of ketamine. Neuropsychopharmacology. 2013 Oct;38(11):2268–2277.
  • Fuxe K, Dahlstrom AB, Jonsson G, et al. The discovery of central monoamine neurons gave volume transmission to the wired brain. Prog Neurobiol. 2010 Feb 9;90(2):82–100. doi: 10.1016/j.pneurobio.2009.10.012
  • Borroto-Escuela DO, Agnati LF, Bechter K, et al. The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks. Philos Trans R Soc Lond B Biol Sci. 2015 Jul 5;370(1672):20140183. doi: 10.1098/rstb.2014.0183
  • Jin Z, Han Y, Zhang D, et al. Application of intranasal administration in the delivery of antidepressant active ingredients. Pharmaceutics. 2022 Sep 28;14(10):2070. doi: 10.3390/pharmaceutics14102070
  • Alvarez-Contino JE, Diaz-Sanchez E, Mirchandani-Duque M, et al. GALR2 and Y1R agonists intranasal infusion enhanced adult ventral hippocampal neurogenesis and antidepressant-like effects involving BDNF actions. J Cell Physiol. 2023 Jan 4;238(2):459–474. doi: 10.1002/jcp.30944
  • Sun HL, Zhou ZQ, Zhang GF, et al. Role of hippocampal p11 in the sustained antidepressant effect of ketamine in the chronic unpredictable mild stress model. Transl Psychiatry. 2016 Feb 23;6(2):e741. doi: 10.1038/tp.2016.21
  • Sabban EL, Serova LI. Potential of intranasal neuropeptide Y (NPY) and/or melanocortin 4 receptor (MC4R) antagonists for preventing or treating PTSD. Mil Med. 2018 Mar 1;183(suppl_1):408–412. doi: 10.1093/milmed/usx228
  • Deyama S, Duman RS. Neurotrophic mechanisms underlying the rapid and sustained antidepressant actions of ketamine. Pharmacol Biochem Behav. 2020 Jan;188:172837. doi: 10.1016/j.pbb.2019.172837
  • Perera TD, Coplan JD, Lisanby SH, et al. Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J Neurosci. 2007 May 2;27(18):4894–4901. doi: 10.1523/JNEUROSCI.0237-07.2007
  • Yamada J, Jinno S. Potential link between antidepressant-like effects of ketamine and promotion of adult neurogenesis in the ventral hippocampus of mice. Neuropharmacology. 2019 Nov 1;158:107710. doi: 10.1016/j.neuropharm.2019.107710
  • Choi M, Lee SH, Chang HL, et al. Hippocampal VEGF is necessary for antidepressant-like behaviors but not sufficient for antidepressant-like effects of ketamine in rats. Biochim Biophys Acta. 2016 Jul;1862(7):1247–1254.
  • Michaelsson H, Andersson M, Svensson J, et al. The novel antidepressant ketamine enhances dentate gyrus proliferation with no effects on synaptic plasticity or hippocampal function in depressive-like rats. Acta Physiol (Oxf). 2019 Apr;225(4):e13211.
  • Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006 Jun 15;59(12):1116–1127. doi: 10.1016/j.biopsych.2006.02.013
  • Castren E, Kojima M. Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiol Dis. 2017 Jan;97(Pt B):119–126. doi: 10.1016/j.nbd.2016.07.010
  • Hing B, Sathyaputri L, Potash JB. A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder. Am J Med Genet B Neuropsychiatr Genet. 2018 Mar;177(2):143–167. doi: 10.1002/ajmg.b.32616
  • Dwivedi Y. Involvement of brain-derived neurotrophic factor in late-life depression. Am J Geriatr Psychiatry. 2013 May;21(5):433–449. doi: 10.1016/j.jagp.2012.10.026
  • Ray MT, Shannon Weickert C, Webster MJ. Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders. Transl Psychiatry. 2014 May 6;4(5):e389. doi: 10.1038/tp.2014.26
  • Youssef MM, Underwood MD, Huang YY, et al. Association of BDNF Val66Met polymorphism and brain BDNF levels with major depression and suicide. Int J Neuropsychopharmacol. 2018 Jun 1;21(6):528–538. doi: 10.1093/ijnp/pyy008
  • Pandey GN, Ren X, Rizavi HS, et al. Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims. Int J Neuropsychopharmacol. 2008 Dec;11(8):1047–1061.
  • Chen B, Dowlatshahi D, MacQueen GM, et al. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry. 2001 Aug 15;50(4):260–265. doi: 10.1016/S0006-3223(01)01083-6
  • Lucas G, Hendolin P, Harkany T, et al. Neurotrophin-4 mediated TrkB activation reinforces morphine-induced analgesia. Nat Neurosci. 2003 Mar;6(3):221–222.
  • Monteggia LM, Barrot M, Powell CM, et al. Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10827–10832. doi: 10.1073/pnas.0402141101
  • Adachi M, Barrot M, Autry AE, et al. Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy. Biol Psychiatry. 2008 Apr 1;63(7):642–649. doi: 10.1016/j.biopsych.2007.09.019
  • Li Y, Luikart BW, Birnbaum S, et al. TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron. 2008 Aug 14;59(3):399–412. doi: 10.1016/j.neuron.2008.06.023
  • Heilig M, Soderpalm B, Engel JA, et al. Centrally administered neuropeptide Y (NPY) produces anxiolytic-like effects in animal anxiety models. Psychopharmacol (Berl). 1989;98(4):524–529. doi: 10.1007/BF00441953
  • Redrobe JP, Dumont Y, Fournier A, et al. Role of serotonin (5-HT) in the antidepressant-like properties of neuropeptide Y (NPY) in the mouse forced swim test. Peptides. 2005 Aug;26(8):1394–1400.