Skip to main content
SpringerLink
Log in

Ketamine counteracts sevoflurane-induced depressive-like behavior and synaptic plasticity impairments through the adenosine A2A receptor/ERK pathway in rats

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Ketamine is an ionic glutamic acid N-methyl-d-aspartate receptor (NMDAR) antagonist commonly used in clinical anesthesia, and its rapid and lasting antidepressant effect has stimulated great interest in psychology research. However, the molecular mechanisms underlying its antidepressant action are still undetermined. Sevoflurane exposure early in life might induce developmental neurotoxicity and mood disorders. In this study, we evaluated the effect of ketamine against sevoflurane-induced depressive-like behavior and the underlying molecular mechanisms. Here, we reported that A2AR protein expression was upregulated in rats with depression induced by sevoflurane inhalation, which was reversed by ketamine. Pharmacological experiments showed that A2AR agonists could reverse the antidepressant effect of ketamine, decrease extracellular signal-regulated kinase (ERK) phosphorylation, reduce synaptic plasticity, and induce depressive-like behavior. Our results suggest that ketamine mediates ERK1/2 phosphorylation by downregulating A2AR expression and that p-ERK1/2 increases the production of synaptic-associated proteins, enhancing synaptic plasticity in the hippocampus and thereby ameliorating the depressive-like behavior induced by sevoflurane inhalation in rats. This research provides a framework for reducing anesthesia-induced developmental neurotoxicity and developing new antidepressants.

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

Access this article

Log in via an institution

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Lenze EJ, Farber NB, Kharasch E, Schweiger J, Yingling M, Olney J, Newcomer JW (2016) Ninety-six hour ketamine infusion with co-administered clonidine for treatment-resistant depression: a pilot randomised controlled trial. World J Biol Psychiatry 17(3):230–238. https://doi.org/10.3109/15622975.2016.1142607

    Article  PubMed  PubMed Central  Google Scholar 

  2. Dwyer JB, Landeros-Weisenberger A, Johnson JA, Londono Tobon A, Flores JM, Nasir M, Couloures K, Sanacora G, Bloch MH (2021) Efficacy of intravenous ketamine in adolescent treatment-resistant depression: a randomized midazolam-controlled trial. Am J Psychiatry 178(4):352–362. https://doi.org/10.1176/appi.ajp.2020.20010018

    Article  PubMed  Google Scholar 

  3. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47(4):351–354. https://doi.org/10.1016/s0006-3223(99)00230-9

    Article  CAS  PubMed  Google Scholar 

  4. Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, Alkondon M, Yuan P, Pribut HJ, Singh NS, Dossou KS, Fang Y, Huang XP, Mayo CL, Wainer IW, Albuquerque EX, Thompson SM, Thomas CJ, Zarate CA Jr, Gould TD (2016) NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature 533(7604):481–486. https://doi.org/10.1038/nature17998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Abdallah CG, Dutta A, Averill CL, McKie S, Akiki TJ, Averill LA, Deakin JFW (2018) Ketamine, but not the NMDAR antagonist Lanicemine, increases Prefrontal Global Connectivity in Depressed Patients. Chronic Stress (Thousand Oaks) 2. https://doi.org/10.1177/2470547018796102

  6. Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB (2015) Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in Depression. Am J Psychiatry 172(10):950–966. https://doi.org/10.1176/appi.ajp.2015.15040465

    Article  PubMed  Google Scholar 

  7. Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU (2016) Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychol Med 46(7):1459–1472. https://doi.org/10.1017/s0033291716000064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wei MD, Wang YH, Lu K, Lv BJ, Wang Y, Chen WY (2020) Ketamine reverses the impaired fear memory extinction and accompanied depressive-like behaviors in adolescent mice. Behav Brain Res 379:112342. https://doi.org/10.1016/j.bbr.2019.112342

    Article  CAS  PubMed  Google Scholar 

  9. Yang B, Ren Q, Ma M, Chen QX, Hashimoto K (2016) Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the social defeat stress model. Int J Neuropsychopharmacol 19(12). https://doi.org/10.1093/ijnp/pyw080

  10. 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. https://doi.org/10.1016/j.pharmthera.2019.02.017

    Article  CAS  PubMed  Google Scholar 

  11. Liang L, Xie R, Lu R, Ma R, Wang X, Wang F, Liu B, Wu S, Wang Y, Zhang H (2020) Involvement of homodomain interacting protein kinase 2-c-Jun N-terminal kinase/c-Jun cascade in the long-term synaptic toxicity and cognition impairment induced by neonatal sevoflurane exposure. J Neurochem 154(4):372–388. https://doi.org/10.1111/jnc.14910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xiao H, Liu B, Chen Y, Zhang J (2016) Learning, memory and synaptic plasticity in hippocampus in rats exposed to sevoflurane. Int J Dev Neurosci 48:38–49. https://doi.org/10.1016/j.ijdevneu.2015.11.001

    Article  CAS  PubMed  Google Scholar 

  13. Vutskits L, Xie Z (2016) Lasting impact of general anaesthesia on the brain: mechanisms and relevance. Nat Rev Neurosci 17(11):705–717. https://doi.org/10.1038/nrn.2016.128

    Article  CAS  PubMed  Google Scholar 

  14. Soriano SG, Vutskits L, Jevtovic-Todorovic V, Hemmings HC (2017) Thinking, fast and slow: highlights from the 2016 BJA seminar on anaesthetic neurotoxicity and neuroplasticity. Br J Anaesth 119(3):443–447. https://doi.org/10.1093/bja/aex238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pavković Ž, Milanović D, Ruždijić S, Kanazir S, Pešić V (2018) The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats. Paediatr Anaesth 28(6):537–546. https://doi.org/10.1111/pan.13396

    Article  PubMed  Google Scholar 

  16. Liu H, Meng X, Li Y, Chen S, Ji Y, Song S, Ji F, Jin X (2022) Neonatal exposure to sevoflurane impairs preference for social novelty in C57BL/6 female mice at early-adulthood. Biochem Biophys Res Commun 593:129–136. https://doi.org/10.1016/j.bbrc.2022.01.022

    Article  CAS  PubMed  Google Scholar 

  17. Jin X, Ji L, Chen Q, Sheng R, Ji F, Yang J (2020) Anesthesia plus surgery in neonatal period impairs preference for social novelty in mice at the juvenile age. Biochem Biophys Res Commun 530(3):603–608. https://doi.org/10.1016/j.bbrc.2020.07.108

    Article  CAS  PubMed  Google Scholar 

  18. Raper J, Alvarado MC, Murphy KL, Baxter MG (2015) Multiple anesthetic exposure in infant monkeys alters emotional reactivity to an Acute Stressor. Anesthesiology 123(5):1084–1092. https://doi.org/10.1097/aln.0000000000000851

    Article  CAS  PubMed  Google Scholar 

  19. Chen Q, Chu W, Sheng R, Song S, Yang J, Ji F, Jin X (2021) Maternal anesthesia with sevoflurane during the mid-gestation induces social interaction deficits in offspring C57BL/6 mice. Biochem Biophys Res Commun 553:65–71. https://doi.org/10.1016/j.bbrc.2021.03.063

    Article  CAS  PubMed  Google Scholar 

  20. Oliveros A, Cho CH, Cui A, Choi S, Lindberg D, Hinton D, Jang MH, Choi DS (2017) Adenosine A(2A) receptor and ERK-driven impulsivity potentiates hippocampal neuroblast proliferation. Transl Psychiatry 7(4):e1095. https://doi.org/10.1038/tp.2017.64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kaster MP, Machado DG, Santos AR, Rodrigues AL (2012) Involvement of NMDA receptors in the antidepressant-like action of adenosine. Pharmacol Rep 64(3):706–713. https://doi.org/10.1016/s1734-1140(12)70865-4

    Article  CAS  PubMed  Google Scholar 

  22. El Yacoubi M, Ledent C, Parmentier M, Costentin J, Vaugeois JM (2000) The anxiogenic-like effect of caffeine in two experimental procedures measuring anxiety in the mouse is not shared by selective A(2A) adenosine receptor antagonists. Psychopharmacology 148(2):153–163. https://doi.org/10.1007/s002130050037

    Article  PubMed  Google Scholar 

  23. Jain N, Kemp N, Adeyemo O, Buchanan P, Stone TW (1995) Anxiolytic activity of adenosine receptor activation in mice. Br J Pharmacol 116(3):2127–2133. https://doi.org/10.1111/j.1476-5381.1995.tb16421.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Al-Attraqchi OHA, Attimarad M, Venugopala KN, Nair A, Al-Attraqchi NHA (2019) Adenosine A2A receptor as a potential drug target - current status and future perspectives. Curr Pharm Des 25(25):2716–2740. https://doi.org/10.2174/1381612825666190716113444

    Article  CAS  PubMed  Google Scholar 

  25. Yamada K, Kobayashi M, Shiozaki S, Ohta T, Mori A, Jenner P, Kanda T (2014) Antidepressant activity of the adenosine A2A receptor antagonist, istradefylline (KW-6002) on learned helplessness in rats. Psychopharmacology 231(14):2839–2849. https://doi.org/10.1007/s00213-014-3454-0

    Article  CAS  PubMed  Google Scholar 

  26. Yamada K, Kobayashi M, Mori A, Jenner P, Kanda T (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  CAS  PubMed  Google Scholar 

  27. El Yacoubi M, Ledent C, Parmentier M, Bertorelli R, Ongini E, Costentin J, Vaugeois JM (2001) Adenosine A2A receptor antagonists are potential antidepressants: evidence based on pharmacology and A2A receptor knockout mice. Br J Pharmacol 134(1):68–77. https://doi.org/10.1038/sj.bjp.0704240

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wang JQ, Mao L (2019) The ERK Pathway: Molecular Mechanisms and Treatment of Depression. Mol Neurobiol 56(9):6197–6205. https://doi.org/10.1007/s12035-019-1524-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wu Z, Li X, Zhang Y, Tong D, Wang L, Zhao P (2018) Effects of Sevoflurane exposure during mid-pregnancy on learning and memory in offspring rats: Beneficial Effects of maternal Exercise. Front Cell Neurosci 12:122. https://doi.org/10.3389/fncel.2018.00122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Oh DR, Yoo JS, Kim Y, Kang H, Lee H, Lm SJ, Choi EJ, Jung MA, Bae D, Oh KN, Hong JA, Jo A, Shin J, Kim J, Kim YR, Cho SS, Lee BJ, Choi CY (2018) Vaccinium bracteatum Leaf Extract reverses chronic Restraint Stress-Induced Depression-Like Behavior in mice: regulation of hypothalamic-pituitary-adrenal Axis, serotonin turnover Systems, and ERK/Akt phosphorylation. Front Pharmacol 9:604. https://doi.org/10.3389/fphar.2018.00604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lee CW, Chen YJ, Wu HF, Chung YJ, Lee YC, Li CT, Lin HC (2019) Ketamine ameliorates severe traumatic event-induced antidepressant-resistant depression in a rat model through ERK activation. Prog Neuropsychopharmacol Biol Psychiatry 93:102–113. https://doi.org/10.1016/j.pnpbp.2019.03.015

    Article  CAS  PubMed  Google Scholar 

  32. Gorain B, Choudhury H, Yee GS, Bhattamisra SK (2019) Adenosine receptors as novel targets for the treatment of various cancers. Curr Pharm Des 25(26):2828–2841. https://doi.org/10.2174/1381612825666190716102037

    Article  CAS  PubMed  Google Scholar 

  33. Chang D, Zhao J, Zhang X, Lian H, Du X, Yuan R, Wen Y, Gao L (2019) Effect of ketamine combined with DHA on lipopolysaccharide-induced depression-like behavior in rats. Int Immunopharmacol 75:105788. https://doi.org/10.1016/j.intimp.2019.105788

    Article  CAS  PubMed  Google Scholar 

  34. Wu Q, Chen J, Yue J, Ying X, Zhou Y, Chen X, Tu W, Lou X, Yang G, Zhou K, Jiang S (2021) Electroacupuncture improves neuronal plasticity through the A2AR/cAMP/PKA signaling pathway in SNL rats. Neurochem Int 145:104983. https://doi.org/10.1016/j.neuint.2021.104983

    Article  CAS  PubMed  Google Scholar 

  35. Al-Griw MA, Alghazeer RO, Awayn N, Shamlan G, Eskandrani AA, Alnajeebi AM, Babteen NA, Alansari WS (2021) Selective adenosine A(2A) receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats. Saudi J Biol Sci 28(1):310–316. https://doi.org/10.1016/j.sjbs.2020.09.063

    Article  CAS  PubMed  Google Scholar 

  36. Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 463(1–3):3–33. https://doi.org/10.1016/s0014-2999(03)01272-x

    Article  CAS  PubMed  Google Scholar 

  37. Gao QS, Zhang YH, Xue H, Wu ZY, Li C, Zhao P (2021) Brief inhalation of sevoflurane can reduce glial scar formation after hypoxic-ischemic brain injury in neonatal rats. Neural Regen Res 16(6):1052–1061. https://doi.org/10.4103/1673-5374.300456

    Article  CAS  PubMed  Google Scholar 

  38. Kraeuter AK, Guest PC, Sarnyai Z (2019) The forced swim test for Depression-Like Behavior in rodents. Methods Mol Biol 1916:75–80. https://doi.org/10.1007/978-1-4939-8994-2_5

    Article  CAS  PubMed  Google Scholar 

  39. Armario A (2021) The forced swim test: historical, conceptual and methodological considerations and its relationship with individual behavioral traits. Neurosci Biobehav Rev 128:74–86. https://doi.org/10.1016/j.neubiorev.2021.06.014

    Article  PubMed  Google Scholar 

  40. Jiang P, Guo Y, Dang R, Yang M, Liao D, Li H, Sun Z, Feng Q, Xu P (2017) Salvianolic acid B protects against lipopolysaccharide-induced behavioral deficits and neuroinflammatory response: involvement of autophagy and NLRP3 inflammasome. J Neuroinflamm 14(1):239. https://doi.org/10.1186/s12974-017-1013-4

    Article  CAS  Google Scholar 

  41. Song AQ, Gao B, Fan JJ, Zhu YJ, Zhou J, Wang YL, Xu LZ, Wu WN (2020) NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice. J Neuroinflamm 17(1):178. https://doi.org/10.1186/s12974-020-01848-8

    Article  CAS  Google Scholar 

  42. Satomoto M, Satoh Y, Terui K, Miyao H, Takishima K, Ito M, Imaki J (2009) Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 110(3):628–637. https://doi.org/10.1097/ALN.0b013e3181974fa2

    Article  CAS  PubMed  Google Scholar 

  43. Chung W, Park S, Hong J, Park S, Lee S, Heo J, Kim D, Ko Y (2015) Sevoflurane exposure during the neonatal period induces long-term memory impairment but not autism-like behaviors. Paediatr Anaesth 25(10):1033–1045. https://doi.org/10.1111/pan.12694

    Article  PubMed  Google Scholar 

  44. Tao G, Zhang J, Zhang L, Dong Y, Yu B, Crosby G, Culley DJ, Zhang Y, Xie Z (2014) Sevoflurane induces tau phosphorylation and glycogen synthase kinase 3β activation in young mice. Anesthesiology 121(3):510–527. https://doi.org/10.1097/aln.0000000000000278

    Article  CAS  PubMed  Google Scholar 

  45. Ju LS, Jia M, Sun J, Sun XR, Zhang H, Ji MH, Yang JJ, Wang ZY (2016) Hypermethylation of hippocampal synaptic plasticity-related genes is involved in neonatal sevoflurane Exposure-Induced cognitive impairments in rats. Neurotox Res 29(2):243–255. https://doi.org/10.1007/s12640-015-9585-1

    Article  CAS  PubMed  Google Scholar 

  46. Kong F, Zhang Y, Wang T, Zhong L, Feng C, Wu Y (2023) Repeated sevoflurane exposures inhibit neurogenesis by inducing the upregulation of glutamate transporter 1 in astrocytes. Eur J Neurosci 57(2):217–232. https://doi.org/10.1111/ejn.15874

    Article  CAS  PubMed  Google Scholar 

  47. Fan XY, Shi G, Zhao P (2021) Neonatal sevoflurane exposure impairs learning and memory by the hypermethylation of hippocampal synaptic genes. Mol Neurobiol 58(3):895–904. https://doi.org/10.1007/s12035-020-02161-4

    Article  CAS  PubMed  Google Scholar 

  48. Zhao X, Shi D, Du Y, Hu C, Li Y, Liu J, Pan C (2022) Repeated neonatal exposure to Sevoflurane induces age-dependent impairments in cognition and synaptic plasticity in mice. Dev Neurosci 44(3):153–161. https://doi.org/10.1159/000523730

    Article  CAS  PubMed  Google Scholar 

  49. Wu Y, Yang Z, Su S, Xu X, Li Y, Li X, Gao Y, Sun D, Wan S, Pen M, Jin W, Ke C (2022) Differential epitranscriptome and proteome modulation in the brain of neonatal mice exposed to isoflurane or sevoflurane. Cell Biol Toxicol. https://doi.org/10.1007/s10565-022-09701-9

    Article  PubMed  PubMed Central  Google Scholar 

  50. Singh JB, Fedgchin M, Daly EJ, De Boer P, Cooper K, Lim P, Pinter C, Murrough JW, Sanacora G, Shelton RC, Kurian B, Winokur A, Fava M, Manji H, Drevets WC, Van Nueten L (2016) A Double-Blind, randomized, Placebo-Controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry 173(8):816–826. https://doi.org/10.1176/appi.ajp.2016.16010037

    Article  PubMed  Google Scholar 

  51. Phillips JL, Norris S, Talbot J, Birmingham M, Hatchard T, Ortiz A, Owoeye O, Batten LA, Blier P (2019) Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: a Randomized Controlled Trial. Am J Psychiatry 176(5):401–409. https://doi.org/10.1176/appi.ajp.2018.18070834

    Article  PubMed  Google Scholar 

  52. Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, Jha MK, Horn SR, Kautz M, Corniquel M, Collins KA, Bevilacqua L, Glasgow AM, Brallier J, Pietrzak RH, Murrough JW, Charney DS (2021) A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder. Am J Psychiatry 178(2):193–202. https://doi.org/10.1176/appi.ajp.2020.20050596

    Article  PubMed  Google Scholar 

  53. Zhang F, Luo J, Zhu X (2018) Ketamine ameliorates depressive-like behaviors by tPA-mediated conversion of proBDNF to mBDNF in the hippocampus of stressed rats. Psychiatry Res 269:646–651. https://doi.org/10.1016/j.psychres.2018.08.075

    Article  CAS  PubMed  Google Scholar 

  54. Cui Y, Hu S, Hu H (2019) Lateral Habenular Burst Firing as a target of the Rapid Antidepressant Effects of ketamine. Trends Neurosci 42(3):179–191. https://doi.org/10.1016/j.tins.2018.12.002

    Article  CAS  PubMed  Google Scholar 

  55. Kim JW, Monteggia LM (2020) Increasing doses of ketamine curtail antidepressant responses and suppress associated synaptic signaling pathways. Behav Brain Res 380:112378. https://doi.org/10.1016/j.bbr.2019.112378

    Article  CAS  PubMed  Google Scholar 

  56. Simonini A, Brogi E, Cascella M, Vittori A (2022) Advantages of ketamine in pediatric anesthesia. Open Med (Warsaw Poland) 17(1):1134–1147. https://doi.org/10.1515/med-2022-0509

    Article  CAS  Google Scholar 

  57. Dwivedi P, Patel TK, Bajpai V, Singh Y, Tripathi A, Kishore S (2022) Efficacy and safety of intranasal ketamine compared with intranasal dexmedetomidine as a premedication before general anesthesia in pediatric patients: a systematic review and meta-analysis of randomized controlled trials. Can J anaesthesia = Journal canadien d’anesthesie 69(11):1405–1418. https://doi.org/10.1007/s12630-022-02305-1

    Article  CAS  Google Scholar 

  58. Nelson ST, Hsiao L, Turgeon SM (2019) Sex and housing conditions modify the effects of adolescent caffeine exposure on anxiety-like and depressive-like behavior in the rat. Behav Pharmacol 30(7):539–546. https://doi.org/10.1097/fbp.0000000000000489

    Article  CAS  PubMed  Google Scholar 

  59. Mitra S, Santana Miranda V, McMillan C, Dykes D, Mucha M, Marth TE, Poe B, Basu DG, Bult-Ito A (2020) Trait specific modulatory effects of caffeine exposure on compulsive-like behaviors in a spontaneous mouse model of obsessive-compulsive disorder. Behav Pharmacol 31(7):622–632. https://doi.org/10.1097/fbp.0000000000000570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Szopa A, Bogatko K, Serefko A, Wyska E, Wośko S, Świąder K, Doboszewska U, Wlaź A, Wróbel A, Wlaź P, Dudka J, Poleszak E (2019) Agomelatine and tianeptine antidepressant activity in mice behavioral despair tests is enhanced by DMPX, a selective adenosine A(2A) receptor antagonist, but not DPCPX, a selective adenosine A(1) receptor antagonist. Pharmacol Rep 71(4):676–681. https://doi.org/10.1016/j.pharep.2019.03.007

    Article  CAS  PubMed  Google Scholar 

  61. Vaz SH, Lérias SR, Parreira S, Diógenes MJ, Sebastião AM (2015) Adenosine A2A receptor activation is determinant for BDNF actions upon GABA and glutamate release from rat hippocampal synaptosomes. Purinergic Signal 11(4):607–612. https://doi.org/10.1007/s11302-015-9476-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Li XC, Hong FF, Tu YJ, Li YA, Ma CY, Yu CY, Fang L, Chen JY, Li ZL, Bao SJ, Zhang ZL, Ying HY, Gyabaah AT, Hu SY, Shao GH, Cai XH (2022) Blockade of adenosine A(2A) receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice. Exp Neurol 350:113929. https://doi.org/10.1016/j.expneurol.2021.113929

    Article  CAS  PubMed  Google Scholar 

  63. Ribeiro FF, Ferreira F, Rodrigues RS, Soares R, Pedro DM, Duarte-Samartinho M, Aroeira RI, Ferreiro E, Valero J, Solá S, Mira H, Sebastião AM, Xapelli S (2021) Regulation of hippocampal postnatal and adult neurogenesis by adenosine A(2A) receptor: Interaction with brain-derived neurotrophic factor. Stem Cells 39(10):1362–1381. https://doi.org/10.1002/stem.3421

    Article  CAS  PubMed  Google Scholar 

  64. Carvalho K, Faivre E, Pietrowski MJ, Marques X, Gomez-Murcia V, Deleau A, Huin V, Hansen JN, Kozlov S, Danis C, Temido-Ferreira M, Coelho JE, Mériaux C, Eddarkaoui S, Gras SL, Dumoulin M, Cellai L, Landrieu I, Chern Y, Hamdane M, Buée L, Boutillier AL, Levi S, Halle A, Lopes LV, Blum D (2019) Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pathology linked to neuronal adenosine A2A receptor. Brain 142(11):3636–3654. https://doi.org/10.1093/brain/awz288

    Article  PubMed  PubMed Central  Google Scholar 

  65. Lin S, Li Q, Jiang S, Xu Z, Jiang Y, Liu L, Jiang J, Tong Y, Wang P (2021) Crocetin ameliorates chronic restraint stress-induced depression-like behaviors in mice by regulating MEK/ERK pathways and gut microbiota. J Ethnopharmacol 268:113608. https://doi.org/10.1016/j.jep.2020.113608

    Article  CAS  PubMed  Google Scholar 

  66. Zhong X, Li G, Qiu F, Huang Z (2018) Paeoniflorin ameliorates chronic Stress-Induced Depression-Like Behaviors and neuronal damages in rats via activation of the ERK-CREB pathway. Front Psychiatry 9:772. https://doi.org/10.3389/fpsyt.2018.00772

    Article  PubMed  Google Scholar 

  67. Sierra-Fonseca JA, Parise LF, Flores-Ramirez FJ, Robles EH, Garcia-Carachure I, Iñiguez SD (2019) Dorsal Hippocampus ERK2 Signaling mediates anxiolytic-related behavior in male rats. Chronic Stress (Thousand Oaks) 3. https://doi.org/10.1177/2470547019897030

  68. Lu J, Zhou H, Meng D, Zhang J, Pan K, Wan B, Miao Z (2020) Tanshinone IIA improves Depression-like Behavior in mice by activating the ERK-CREB-BDNF signaling pathway. Neuroscience 430:1–11. https://doi.org/10.1016/j.neuroscience.2020.01.026

    Article  CAS  PubMed  Google Scholar 

  69. Humo M, Ayazgök B, Becker LJ, Waltisperger E, Rantamäki T, Yalcin I (2020) Ketamine induces rapid and sustained antidepressant-like effects in chronic pain induced depression: role of MAPK signaling pathway. Prog Neuropsychopharmacol Biol Psychiatry 100:109898. https://doi.org/10.1016/j.pnpbp.2020.109898

    Article  CAS  PubMed  Google Scholar 

  70. Sowa J, Kusek M, Bobula B, Hess G, Tokarski K (2019) Ketamine Administration Reverses Corticosterone-Induced Alterations in Excitatory and Inhibitory Transmission in the Rat Dorsal Raphe Nucleus. Neural Plast 2019:3219490. doi:https://doi.org/10.1155/2019/3219490

  71. Yang Y, Song Y, Zhang X, Zhao W, Ma T, Liu Y, Ma P, Zhao Y, Zhang H (2020) Ketamine relieves depression-like behaviors induced by chronic postsurgical pain in rats through anti-inflammatory, anti-oxidant effects and regulating BDNF expression. Psychopharmacology 237(6):1657–1669. https://doi.org/10.1007/s00213-020-05490-3

    Article  CAS  PubMed  Google Scholar 

  72. Atef RM, Agha AM, Abdel-Rhaman A-RA, Nassar NN (2018) The Ying and Yang of Adenosine A1 and A2A receptors on ERK1/2 activation in a rat model of Global Cerebral Ischemia Reperfusion Injury. Mol Neurobiol 55(2):1284–1298. https://doi.org/10.1007/s12035-017-0401-1

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

This work was supported by the National Natural Science Foundation of China (No. 82271296 to Ping Zhao and No. 82001154 to Ziyi Wu) and Natural Science Foundation of Liaoning Province (No. 2021-MS-157 to Weiwei Yu).

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China

    Weiwei Yu, Ziyi Wu, Xingyue Li, Mengmeng Ding, Ying Xu & Ping Zhao

Authors
  1. Weiwei Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ziyi Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xingyue Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mengmeng Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ping Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Weiwei Yu and Ping Zhao designed the study; Weiwei Yu and Mengmeng Ding performed the investigation; Weiwei Yu and Ziyi Wu analyzed the data; and Weiwei Yu, Ying Xu, and Xingyue Li wrote the manuscript.

Corresponding author

Correspondence to Ping Zhao.

Ethics declarations

Competing Interests

The authors declare that they have no conflict of interest.

Ethics Approval

All animal experimental protocols were approved by the Institutional Animal Care and Use Committee of Shengjing Hospital, China Medical University (IACUC no. 2021PS832K).

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Additional information

Publisher’s Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, W., Wu, Z., Li, X. et al. Ketamine counteracts sevoflurane-induced depressive-like behavior and synaptic plasticity impairments through the adenosine A2A receptor/ERK pathway in rats. Mol Neurobiol 60, 6160–6175 (2023). https://doi.org/10.1007/s12035-023-03474-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-023-03474-w

Keywords

Search

Navigation