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The antidepressant-like effect of guanosine involves the modulation of adenosine A1 and A2A receptors

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Abstract

Guanosine has been considered a promising candidate for antidepressant responses, but if this nucleoside could modulate adenosine A1 (A1R) and A2A (A2AR) receptors to exert antidepressant-like actions remains to be elucidated. This study investigated the role of A1R and A2AR in the antidepressant-like response of guanosine in the mouse tail suspension test and molecular interactions between guanosine and A1R and A2AR by docking analysis. The acute (60 min) administration of guanosine (0.05 mg/kg, p.o.) significantly decreased the immobility time in the tail suspension test, without affecting the locomotor performance in the open-field test, suggesting an antidepressant-like effect. This behavioral response was paralleled with increased A1R and reduced A2AR immunocontent in the hippocampus, but not in the prefrontal cortex, of mice. Guanosine-mediated antidepressant-like effect was not altered by the pretreatment with caffeine (3 mg/kg, i.p., a non-selective adenosine A1R/A2AR antagonist), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX — 2 mg/kg, i.p., a selective adenosine A1R antagonist), or 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)-phenol (ZM241385 — 1 mg/kg, i.p., a selective adenosine A2AR antagonist). However, the antidepressant-like response of guanosine was completely abolished by adenosine (0.5 mg/kg, i.p., a non-selective adenosine A1R/A2AR agonist), N-6-cyclohexyladenosine (CHA — 0.05 mg/kg, i.p., a selective adenosine A1 receptor agonist), and N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA — 0.1 mg/kg, i.p., a selective adenosine A2A receptor agonist). Finally, docking analysis also indicated that guanosine might interact with A1R and A2AR at the adenosine binding site. Overall, this study reinforces the antidepressant-like of guanosine and unveils a previously unexplored modulation of the modulation of A1R and A2AR in its antidepressant-like effect.

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Data availability

All data generated or analyzed during this study are included in this published article.

References

  1. World Health Organization (2017) Depression and other common mental disorders: global health estimates. World Health Organization 1–24

  2. Otte C, Gold S, Penninx B et al (2016) Major depressive disorder. Nat Rev Dis Primers 2:1–20. https://doi.org/10.1038/nrdp.2016.65

    Article  Google Scholar 

  3. Kaster MP, Moretti M, Cunha MP, Rodrigues ALS (2016) Novel approaches for the management of depressive disorders. Eur J Pharmacol 771:236–240. https://doi.org/10.1016/j.ejphar.2015.12.029

    Article  CAS  PubMed  Google Scholar 

  4. Papakostas GI, Ionescu DF (2015) Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder. Mol Psychiatry 20:1142–1150. https://doi.org/10.1038/mp.2015.92

    Article  CAS  PubMed  Google Scholar 

  5. Bartoli F, Burnstock G, Crocamo C, Carrà G (2020) Purinergic signaling and related biomarkers in depression. Brain Sci 10:1–12. https://doi.org/10.3390/BRAINSCI10030160

    Article  Google Scholar 

  6. Szopa A, Socała K, Serefko A et al (2021) Purinergic transmission in depressive disorders. Pharmacol Ther 224:107821. https://doi.org/10.1016/J.PHARMTHERA.2021.107821

    Article  CAS  PubMed  Google Scholar 

  7. Burnstock G (2020) Introduction to purinergic signaling. Methods Mol Biol 2041:1–15. https://doi.org/10.1007/978-1-4939-9717-6_1

    Article  CAS  PubMed  Google Scholar 

  8. Fredholm BB, Chen J, Cunha RA, Svenningsson P (2005) Adenosine and brain function. Int Rev Neurobiol 63:7742. https://doi.org/10.1016/S0074-7742(05)63007-3

    Google Scholar 

  9. Gomes JI, Farinha-Ferreira M, Rei N et al (2021) Of adenosine and the blues: the adenosinergic system in the pathophysiology and treatment of major depressive disorder. Pharmacol Res 163:105363. https://doi.org/10.1016/J.PHRS.2020.105363

    Article  CAS  PubMed  Google Scholar 

  10. Kaster MP, Rosa AO, Rosso MM et al (2004) Adenosine administration produces an antidepressant-like effect in mice: evidence for the involvement of A1 and A2A receptors. Neurosci Lett 355:21–24. https://doi.org/10.1016/J.NEULET.2003.10.040

    Article  CAS  PubMed  Google Scholar 

  11. Kaster MP, Machado NJ, Silva HB et al (2015) Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress. Proceed National Acad Sci USA 112:7833–7838. https://doi.org/10.1073/pnas.1423088112

    Article  CAS  Google Scholar 

  12. van Calker D, Biber K, Domschke K, Serchov T (2019) The role of adenosine receptors in mood and anxiety disorders. J Neurochem 151:11–27. https://doi.org/10.1111/JNC.14841

    Article  PubMed  Google Scholar 

  13. Cunha MP, Pazini FL, Rosa JM et al (2015) Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A1and A2Areceptor activation. Purinergic Signalling 11:215–227. https://doi.org/10.1007/s11302-015-9446-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lobato KR, Binfaré RW, Budni J et al (2008) Involvement of the adenosine A1 and A2A receptors in the antidepressant-like effect of zinc in the forced swimming test. Prog Neuropsychopharmacol Biol Psychiatry 32:994–999. https://doi.org/10.1016/J.PNPBP.2008.01.012

    Article  CAS  PubMed  Google Scholar 

  15. Lazarevic V, Yang Y, Flais I, Svenningsson P (2021) Ketamine decreases neuronally released glutamate via retrograde stimulation of presynaptic adenosine A1 receptors. Mole Psychiatry 26(12):7425–7435. https://doi.org/10.1038/s41380-021-01246-3

    Article  CAS  Google Scholar 

  16. Camargo A, Rodrigues ALS (2022) Guanosine as a promising target for fast-acting antidepressant responses. Pharmacol Biochem Behav 218:173422. https://doi.org/10.1016/J.PBB.2022.173422

    Article  CAS  PubMed  Google Scholar 

  17. Almeida RF, Ferreira TP, David CVC et al (2021) Guanine-based purines as an innovative target to treat major depressive disorder. Front Pharmacol 547:1–6. https://doi.org/10.3389/FPHAR.2021.652130

    Article  Google Scholar 

  18. di Liberto V, Mudò G, Garozzo R et al (2016) The guanine-based purinergic system: The tale of an orphan neuromodulation. Front Pharmacol 7:1–15. https://doi.org/10.3389/fphar.2016.00158

    Article  Google Scholar 

  19. Bettio LEB, Gil-Mohapel J, Rodrigues ALS (2016) Guanosine and its role in neuropathologies. Purinergic Signalling 12:411–426. https://doi.org/10.1007/s11302-016-9509-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lanznaster D, Dal-Cim T, Piermartiri TCB, Tasca CI (2016) Guanosine: a neuromodulator with therapeutic potential in brain disorders. Aging Dis 7:657–679. https://doi.org/10.14336/AD.2016.0208

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ali-Sisto T, Tolmunen T, Toffol E et al (2016) Purine metabolism is dysregulated in patients with major depressive disorder. Psychoneuroendocrinology 70:25–32. https://doi.org/10.1016/j.psyneuen.2016.04.017

    Article  CAS  PubMed  Google Scholar 

  22. Mocking RJT, Naviaux JC, Li K et al (2021) Metabolic features of recurrent major depressive disorder in remission, and the risk of future recurrence. Translational Psychiatry 11(1):1–13. https://doi.org/10.1038/s41398-020-01182-w

    Article  CAS  Google Scholar 

  23. Almeida RF, Pocharski CB, Rodrigues ALS et al (2020) Guanosine fast onset antidepressant-like effects in the olfactory bulbectomy mice model. Sci Rep 10:8429. https://doi.org/10.1038/s41598-020-65300-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bettio LEB, Cunha MP, Budni J et al (2012) Guanosine produces an antidepressant-like effect through the modulation of NMDA receptors, nitric oxide-cGMP and PI3K/mTOR pathways. Behav Brain Res 234:137–148. https://doi.org/10.1016/j.bbr.2012.06.021

    Article  CAS  PubMed  Google Scholar 

  25. Rosa PB, Bettio LEB, Neis VB et al (2021) Antidepressant-like effect of guanosine involves activation of AMPA receptor and BDNF/TrkB signaling. Purinergic Signal 17:285–301. https://doi.org/10.1007/s11302-021-09779-6

  26. Rosa PB, Bettio LEB, Neis VB et al (2019) The antidepressant-like effect of guanosine is dependent on GSK-3β inhibition and activation of MAPK/ERK and Nrf2/heme oxygenase-1 signaling pathways. Purinergic Signalling 15:491–504. https://doi.org/10.1007/s11302-019-09681-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Camargo A, Dalmagro AP, Zeni ALB, Rodrigues ALS (2020) Guanosine potentiates the antidepressant-like effect of subthreshold doses of ketamine: possible role of pro-synaptogenic signaling pathway. J Affect Disord 271:100–108. https://doi.org/10.1016/j.jad.2020.03.186

    Article  CAS  PubMed  Google Scholar 

  28. Almeida RF, Nonose Y, Ganzella M et al (2021) Antidepressant-like effects of chronic guanosine in the olfactory bulbectomy mouse model. Front Psych 1268:1–14. https://doi.org/10.3389/FPSYT.2021.701408

    Article  Google Scholar 

  29. Bettio L, Neis V, Pazini F et al (2016) The antidepressant-like effect of chronic guanosine treatment is associated with increased hippocampal neuronal differentiation. Eur J Neurosci 43:1006–1015. https://doi.org/10.1111/ejn.13172

    Article  PubMed  Google Scholar 

  30. Marques NF, Binder LB, Roversi K et al (2019) Guanosine prevents depressive-like behaviors in rats following bilateral dorsolateral striatum lesion induced by 6-hydroxydopamine. Behav Brain Res 372:112014. https://doi.org/10.1016/j.bbr.2019.112014

    Article  CAS  PubMed  Google Scholar 

  31. Piermartiri T, dos Santos B, Barros-Aragão F et al (2020) Guanosine promotes proliferation in neural stem cells from hippocampus and neurogenesis in adult mice. Mol Neurobiol 57:3814–3826. https://doi.org/10.1007/S12035-020-01977-4

    Article  CAS  PubMed  Google Scholar 

  32. Dal-Cim T, Ludka FK, Martins WC et al (2013) Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions. J Neurochem 126:437–450. https://doi.org/10.1111/jnc.12324

    Article  CAS  PubMed  Google Scholar 

  33. Dal-Cim T, Poluceno GG, Lanznaster D et al (2019) Guanosine prevents oxidative damage and glutamate uptake impairment induced by oxygen/glucose deprivation in cortical astrocyte cultures: involvement of A1 and A2A adenosine receptors and PI3K, MEK, and PKC pathways. Purinergic Signalling 15:465. https://doi.org/10.1007/S11302-019-09679-W

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Massari CM, Constantino LC, Tasca CI (2021) Adenosine A1 and A2A receptors are involved on guanosine protective effects against oxidative burst and mitochondrial dysfunction induced by 6-OHDA in striatal slices. Purinergic Signalling 17:247–254. https://doi.org/10.1007/S11302-021-09765-Y/FIGURES/3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Massari C, Constantino L, Marques N et al (2020) Involvement of adenosine A 1 and A 2A receptors on guanosine-mediated anti-tremor effects in reserpinized mice. Purinergic Signalling 16:379–387. https://doi.org/10.1007/S11302-020-09716-Z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Almeida RF, Comasseto DD, Ramos DB et al (2017) Guanosine anxiolytic-like effect involves adenosinergic and glutamatergic neurotransmitter systems. Mol Neurobiol 54:423–436. https://doi.org/10.1007/s12035-015-9660-x

    Article  CAS  PubMed  Google Scholar 

  37. Frinchi M, Verdi V, Plescia F et al (2020) Guanosine-mediated anxiolytic-like effect: interplay with adenosine A1 and A2A receptors. Int J Mol Sci 21:1–15. https://doi.org/10.3390/IJMS21239281

    Article  Google Scholar 

  38. Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370. https://doi.org/10.1007/BF00428203

    Article  CAS  PubMed  Google Scholar 

  39. Cryan JF, Mombereau C, Vassout A (2005) The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 29:571–625. https://doi.org/10.1016/J.NEUBIOREV.2005.03.009

    Article  CAS  PubMed  Google Scholar 

  40. Dalmagro AP, Camargo A, Rodrigues ALS, Zeni ALB (2019) Involvement of PI3K/Akt/GSK-3β signaling pathway in the antidepressant-like and neuroprotective effects of Morus nigra and its major phenolic, syringic acid. Chem Biol Interact 314:108843. https://doi.org/10.1016/j.cbi.2019.108843

    Article  CAS  PubMed  Google Scholar 

  41. Camargo A, Dalmagro AP, Wolin IAV et al (2021) The resilient phenotype elicited by ketamine against inflammatory stressors-induced depressive-like behavior is associated with NLRP3-driven signaling pathway. J Psychiatr Res 144:118–128. https://doi.org/10.1016/J.JPSYCHIRES.2021.09.057

    Article  PubMed  Google Scholar 

  42. Camargo A, Torrá ACNC, Dalmagro AP et al (2022) Prophylactic efficacy of ketamine, but not the low-trapping NMDA receptor antagonist AZD6765, against stress-induced maladaptive behavior and 4E-BP1-related synaptic protein synthesis impairment. Prog Neuropsychopharmacol Biol Psychiatry 115:110509. https://doi.org/10.1016/J.PNPBP.2022.110509

    Article  CAS  PubMed  Google Scholar 

  43. Camargo A, Dalmagro AP, de Souza MM et al (2020) Ketamine, but not guanosine, as a prophylactic agent against corticosterone-induced depressive-like behavior: possible role of long-lasting pro-synaptogenic signaling pathway. Exp Neurol 334:113459. https://doi.org/10.1016/j.expneurol.2020.113459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Camargo A, Dalmagro AP, Fraga DB et al (2021) Low doses of ketamine and guanosine abrogate corticosterone-induced anxiety-related behavior, but not disturbances in the hippocampal NLRP3 inflammasome pathway. Psychopharmacology 238(9):2555–2568. https://doi.org/10.1007/S00213-021-05879-8

    Article  CAS  PubMed  Google Scholar 

  45. Peterson GLA (1977) A simplification of the protein assay method of Lowry. Anal Biochem 83:346–356. https://doi.org/10.1016/0003-2697(77)90043-4

    Article  CAS  PubMed  Google Scholar 

  46. Camargo A, Dalmagro AP, Wolin IAV et al (2021) A low-dose combination of ketamine and guanosine counteracts corticosterone-induced depressive-like behavior and hippocampal synaptic impairments via mTORC1 signaling. Prog Neuropsychopharmacol Biol Psychiatry 111:110371. https://doi.org/10.1016/j.pnpbp.2021.110371

    Article  CAS  PubMed  Google Scholar 

  47. Fraga DB, Camargo A, Olescowicz G et al (2021) A single administration of ascorbic acid rapidly reverses depressive-like behavior and hippocampal synaptic dysfunction induced by corticosterone in mice. Chem Biol Interact 342:109476. https://doi.org/10.1016/j.cbi.2021.109476

    Article  CAS  PubMed  Google Scholar 

  48. Camargo A, Pazini FL, Rosa JM et al (2019) Augmentation effect of ketamine by guanosine in the novelty-suppressed feeding test is dependent on mTOR signaling pathway. J Psychiatr Res 115:103–112. https://doi.org/10.1016/j.jpsychires.2019.05.017

    Article  PubMed  Google Scholar 

  49. Camargo A, Dalmagro AP, Rosa MJ et al (2020) Subthreshold doses of guanosine plus ketamine elicit antidepressant-like effect in a mouse model of depression induced by corticosterone: Role of GR/NF-κB/IDO-1 signaling. Neurochem Int 139:104797. https://doi.org/10.1016/j.neuint.2020.104797

    Article  CAS  PubMed  Google Scholar 

  50. Guedes IA, Costa LSC, dos Santos KB et al (2021) Drug design and repurposing with DockThor-VS web server focusing on SARS-CoV-2 therapeutic targets and their non-synonym variants. Sci Rep 11:5543. https://doi.org/10.1038/S41598-021-84700-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Laskowski RA, Swindells MB (2011) LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 51:2778–2786. https://doi.org/10.1021/CI200227U/ASSET/IMAGES/LARGE/CI-2011-00227U_0005.JPEG

    Article  CAS  PubMed  Google Scholar 

  52. Lara DR, Schmidt AP, Frizzo MES et al (2001) Effect of orally administered guanosine on seizures and death induced by glutamatergic agents. Brain Res 912:176–180. https://doi.org/10.1016/S0006-8993(01)02734-2

    Article  CAS  PubMed  Google Scholar 

  53. Schmidt AP, Böhmer AE, Schallenberger C et al (2009) Spinal mechanisms of antinociceptive action caused by guanosine in mice. Eur J Pharmacol 613:46–53. https://doi.org/10.1016/j.ejphar.2009.04.018

    Article  CAS  PubMed  Google Scholar 

  54. Bettio LEB, Freitas AE, Neis VB et al (2014) Guanosine prevents behavioral alterations in the forced swimming test and hippocampal oxidative damage induced by acute restraint stress. Pharmacol Biochem Behav 127:7–14. https://doi.org/10.1016/j.pbb.2014.10.002

    Article  CAS  PubMed  Google Scholar 

  55. Liu W, Ge T, Leng Y et al (2017) The role of neural plasticity in depression: from hippocampus to prefrontal cortex. Neural Plast 2017:6871089. https://doi.org/10.1155/2017/6871089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Yamada K, Kobayashi M, Kanda T (2014) Involvement of adenosine A2A receptors in depression and anxiety. Int Rev Neurobiol 119:373–393. https://doi.org/10.1016/B978-0-12-801022-8.00015-5

    Article  PubMed  Google Scholar 

  57. Coelho JE, Alves P, Canas PM et al (2014) Overexpression of adenosine A2A receptors in rats: effects on depression, locomotion, and anxiety. Front Psych 5:1–8. https://doi.org/10.3389/FPSYT.2014.00067

    Article  CAS  Google Scholar 

  58. Serchov T, Clement HW, Schwarz MK et al (2015) Increased signaling via adenosine A1 receptors, sleep deprivation, imipramine, and ketamine inhibit depressive-like behavior via induction of Homer1a. Neuron 87:549–562. https://doi.org/10.1016/J.NEURON.2015.07.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hodgson RA, Bertorelli R, Varty GB et al (2009) Characterization of the potent and highly selective A2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] in rodent models of movement disorders and depression. J Pharmacol Exp Ther 330:294–303. https://doi.org/10.1124/JPET.108.149617

    Article  CAS  PubMed  Google Scholar 

  60. Yamada K, Kobayashi M, Mori A et al (2013) Antidepressant-like activity of the adenosine A(2A) receptor antagonist, istradefylline (KW-6002), in the forced swim test and the tail suspension test in rodents. Pharmacol Biochem Behav 114–115:23–30. https://doi.org/10.1016/J.PBB.2013.10.022

    Article  PubMed  Google Scholar 

  61. Hines DJ, Schmitt LI, Hines RM et al (2013) Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling. Translational Psychiatry 3(1):1–9. https://doi.org/10.1038/tp.2012.136

    Article  Google Scholar 

  62. Lanznaster D, Massari CM, Marková V et al (2019) Adenosine A1–A2A receptor-receptor interaction: contribution to guanosine-mediated effects. Cells 8:1–16. https://doi.org/10.3390/CELLS8121630

    Article  Google Scholar 

  63. Dobrachinski F, Gerbatin RR, Sartori G et al (2019) Guanosine attenuates behavioral deficits after traumatic brain injury by modulation of adenosinergic Receptors. Mol Neurobiol 56:3145–3158. https://doi.org/10.1007/S12035-018-1296-1

    Article  CAS  PubMed  Google Scholar 

  64. Traversa U, Bombi G, di Iorio P et al (2002) Specific [(3)H]-guanosine binding sites in rat brain membranes. Br J Pharmacol 135:969–976. https://doi.org/10.1038/sj.bjp.0704542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Traversa U, Bombi G, Camaioni E et al (2003) Rat brain guanosine binding site: Biological studies and pseudo-receptor construction. Bioorg Med Chem 11:5417–5425. https://doi.org/10.1016/j.bmc.2003.09.043

    Article  CAS  PubMed  Google Scholar 

  66. Jee HJ, Lee SG, Bormate KJ, Jung YS (2020) Effect of caffeine consumption on the risk for neurological and psychiatric disorders: sex differences in Human. Nutrients 12:1–20. https://doi.org/10.3390/NU12103080

    Article  Google Scholar 

  67. Grosso G, Micek A, Castellano S et al (2016) Coffee, tea, caffeine and risk of depression: a systematic review and dose-response meta-analysis of observational studies. Mol Nutr Food Res 60:223–234. https://doi.org/10.1002/MNFR.201500620

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #421143/2018–5 and #312215/2021–5) and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES). ALSR is CNPq Research Fellow.

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  1. Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, FlorianopolisSanta Catarina, 88040-900, Brazil

    Anderson Camargo, Luis E. B. Bettio, Priscila B. Rosa, Julia M. Rosa, Glorister A. Altê & Ana Lúcia S. Rodrigues

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  1. Anderson Camargo
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  2. Luis E. B. Bettio
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  3. Priscila B. Rosa
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Contributions

Ana Lúcia S. Rodrigues designed the study and wrote the protocol. Anderson Camargo, Luis E. B. Bettio, Priscila B. Rosa, and Julia M. Rosa administered the drugs and performed the behavioral tests. Anderson Camargo performed Western blotting analysis. Glorister A. Altê carried out the bioinformatics studies. Anderson Camargo and Ana Lúcia S. Rodrigues contributed to undertake the statistical analysis and wrote the first draft of the manuscript, as well as approved the final manuscript.

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Correspondence to Ana Lúcia S. Rodrigues.

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Camargo, A., Bettio, L.E.B., Rosa, P.B. et al. The antidepressant-like effect of guanosine involves the modulation of adenosine A1 and A2A receptors. Purinergic Signalling 19, 387–399 (2023). https://doi.org/10.1007/s11302-022-09898-8

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