Skip to main content

Advertisement

SpringerLink
Log in

The involvement of GABAergic system in the antidepressant-like effect of agmatine

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Considering the involvement of GABAergic system in the action of the fast-acting antidepressant ketamine, and that agmatine may exert an antidepressant-like effect through mechanisms similar to ketamine, the purpose of the present study was to evaluate the involvement of GABAA and GABAB receptors in the antidepressant-like effect of agmatine. The administration of muscimol (0.1 mg/kg, i.p., GABAA receptor agonist) or diazepam (0.05 mg/kg, p.o., GABAA receptor positive allosteric modulator) at doses that caused no effect in the tail suspension test (TST) combined with a subeffective dose of agmatine (0.0001 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST. In another set of experiments, the administration of baclofen (1 mg/kg, i.p., GABAB receptor agonist) abolished the reduction of immobility time in the TST elicited by agmatine (0.1 mg/kg, p.o., active dose). In another cohort of animals, treatment with NMDA (0.1 pmol/site, i.c.v.) prevented the antidepressant-like effect of the combined administration of agmatine and muscimol as well as ketamine and muscimol in the TST. Results suggest that the effect of agmatine in the TST may involve an activation of GABAA receptors dependent on NMDA receptor inhibition, similar to ketamine, as well as modulation of GABAB receptors.

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

Similar content being viewed by others

References

  • Abdallah CG, Salas R, Jackowski A, Baldwin P, Sato JR, Mathew SJ (2015) Hippocampal volume and the rapid antidepressant effect of ketamine. J Psychopharmacol 29:591–595

    Article  CAS  PubMed  Google Scholar 

  • Andrade C (2017) Ketamine for depression, 5: potential pharmacokinetic and pharmacodynamic drug interactions. J Clin Psychiatry 78:858–861

    Article  Google Scholar 

  • Arranz B, Cowburn R, Eriksson A, Vestling M, Marcusson J (1992) Gamma-aminobutyric acid-B (GABAB) binding sites in postmortem suicide brains. Neuropsychobiology 26:33–36

    Article  CAS  PubMed  Google Scholar 

  • Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475:91–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banasr M, Lepack A, Fee C et al (2017) Characterization of GABAergic marker expression in the chronic unpredictable stress model of depression. Chronic Stress (Thousand Oaks) 1:30

    Google Scholar 

  • Bergfeld IO, Mantione M, Figee M, Schuurman PR, Lok A, Denys D (2018) Treatment-resistant depression and suicidality. J Affect Disord 235:362–367

    Article  CAS  PubMed  Google Scholar 

  • Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354

    Article  CAS  PubMed  Google Scholar 

  • Bettio LE, 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

    Article  CAS  PubMed  Google Scholar 

  • Bhagwagar Z, Wylezinska M, Jezzard P, Evans J, Boorman E, M Matthews P, J Cowen P (2008) Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients. Int J Neuropsychopharmacol 11:255–260

    Article  CAS  PubMed  Google Scholar 

  • Biggio G, Concas A, Corda MG, Giorgi O, Sanna E, Serra M (1990) GABAergic and dopaminergic transmission in the rat cerebral cortex: effect of stress, anxiolytic and anxiogenic drugs. Pharmacol Ther 48:121–142

    Article  CAS  PubMed  Google Scholar 

  • Celada P, Puig M, Amargos-Bosch M et al (2004) The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci 29:252–265

    PubMed  PubMed Central  Google Scholar 

  • Choudary PV, Molnar M, Evans SJ et al (2005) Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci USA 102:15653–15658

  • Clevenger SS, Malhotra D, Dang J, Vanle B, IsHak WW (2018) The role of selective serotonin reuptake inhibitors in preventing relapse of major depressive disorder. Ther Adv Psychopharmacol 8:49–58

    Article  CAS  PubMed  Google Scholar 

  • Cross JA, Cheetham SC, Crompton MR, Katona CLE, Horton RW (1988) Brain GABAB binding sites in depressed suicide victims. Psychiatry Res 26:119–129

    Article  CAS  PubMed  Google Scholar 

  • Cunha MP, Pazini FL, Ludka FK, Rosa JM, Oliveira Á, Budni J, Ramos-Hryb AB, Lieberknecht V, Bettio LEB, Martín-de-Saavedra MD, López MG, Tasca CI, Rodrigues ALS (2015) The modulation of NMDA receptors and L-arginine/nitric oxide pathway is implicated in the anti-immobility effect of creatine in the tail suspension test. Amino Acids 47:795–811

    Article  CAS  PubMed  Google Scholar 

  • Dixit MP, Thakre PP, Pannase AS, Aglawe MM, Taksande BG, Kotagale NR (2014) Imidazoline binding sites mediates anticompulsive-like effect of agmatine in marble-burying behavior in mice. Eur J Pharmacol 732:26–31

    Article  CAS  PubMed  Google Scholar 

  • Farzin D, Mansouri N (2006) Antidepressant-like effect of harmane and other beta-carbolines in the mouse forced swim test. Eur Neuropsychopharmacol 6:324–328

    Article  CAS  Google Scholar 

  • Freitas AE, Bettio LE, Neis VB et al (2014) Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice. Prog Neuro-Psychopharmacol Biol Psychiatry 50:143–150

    Article  CAS  Google Scholar 

  • Gao Y, Zhou JJ, Zhu Y, Wang L, Kosten TA, Zhang X, Li DP (2017) Neuroadaptations of presynaptic and postsynaptic GABAB receptor function in the paraventricular nucleus in response to chronic unpredictable stress. Br J Pharmacol 174:2929–2940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gawali NB, Bulani VD, Chowdhury AA, Deshpande PS, Nagmoti DM, Juvekar AR (2016) Agmatine ameliorates lipopolysaccharide induced depressive-like behaviour in mice by targeting the underlying inflammatory and oxido-nitrosative mediators. Pharmacol Biochem Behav 149:1–8

    Article  CAS  PubMed  Google Scholar 

  • Gawali NB, Bulani VD, Gursahani MS, Deshpande PS, Kothavade PS, Juvekar AR (2017) Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway. Brain Res 1663:66–77

    Article  CAS  PubMed  Google Scholar 

  • Glennon RA, Dukat M, Grella B, Hong SS, Costantino L, Teitler M, Smith C, Egan C, Davis K, Mattson MV (2000) Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors. Drug Alcohol Depend 60:121–132

    Article  CAS  PubMed  Google Scholar 

  • Gomez AF, Barthel AL, Hofmann SG (2018) Comparing the efficacy of benzodiazepines and serotonergic anti-depressants for adults with generalized anxiety disorder: a meta-analytic review. Expert Opin Pharmacother 19:883–894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gray JA, Green AR (1987) Increased GABAB receptor function in mouse frontal cortex after repeated administration of antidepressant drugs or electroconvulsive shocks. Br J Pharmacol 92:357–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardeveld F, Spijker J, De Graaf R et al (2013) Recurrence of major depressive disorder and its predictors in the general population: results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Psychol Med 43:39–48

    Article  CAS  PubMed  Google Scholar 

  • Heinzel A, Steinke R, Poeppel TD, Grosser O, Bogerts B, Otto H, Northoff G (2008) S-ketamine and GABA-A-receptor interaction in humans: an exploratory study with I-123-iomazenil SPECT. Hum Psychopharmacol 23:549–554

    Article  CAS  PubMed  Google Scholar 

  • Hill DR (1985) GABAB receptor modulation of adenylate cyclase activity in rat brain slices. Br J Pharmacol 84:249–257

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kaster MP, Gadotti VM, Calixto JB, Santos ARS, Rodrigues ALS (2012) Depressive-like behavior induced by tumor necrosis factor-alpha in mice. Neuropharmacology 62:419–426

    Article  CAS  PubMed  Google Scholar 

  • Korf J, Venema K (1983) Desmethylimipramine enhances the release of endogenous GABA and other neurotransmitter amino acids from the rat thalamus. J Neurochem 40:946–950

    Article  CAS  PubMed  Google Scholar 

  • Krystal JH, Perry EB Jr, Gueorguieva R et al (2005) Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch Gen Psychiatry 62:985–994

    Article  CAS  PubMed  Google Scholar 

  • Song C, Leonard BE (2005) The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev 29:627–647

    Article  PubMed  Google Scholar 

  • Li NX, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY, Aghajanian G, Duman RS (2011) Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 69:754–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luscher B, Fuchs T (2015) GABAergic control of depression-related brain states. Adv Pharmacol 73:97–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luscher B, Shen Q, Sahir N (2011) The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry 16:383–406

    Article  CAS  PubMed  Google Scholar 

  • Magni G, Garreau M, Orofiamma B et al (1989) Fengabine, a new GABAmimetic agent in the treatment of depressive disorders: an overview of six double-blind studies versus tricyclics. Neuropsychobiology 20:126–131

    Article  CAS  PubMed  Google Scholar 

  • Mathew SJ, Charney DS (2009) Publication bias and the efficacy of antidepressants. Am J Psychiatry 166:140–145

    Article  PubMed  Google Scholar 

  • McCarson KE, Duric V, Reisman SA et al (2006) GABA(B) receptor function and subunit expression in the rat spinal cord as indicators of stress and the antinociceptive response to antidepressants. Brain Res 1068:109–117

    Article  CAS  PubMed  Google Scholar 

  • Meylan EM, Breuillaud L, Seredenina T et al (2016) Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression. Transl Psychiatry 6:1–11

    Article  CAS  Google Scholar 

  • Mohler H (2012) The GABA system in anxiety and depression and its therapeutic potential. Neuropharmacology 62:42–53

    Article  PubMed  CAS  Google Scholar 

  • Moretti M, Neis VB, Matheus FC, Cunha MP, Rosa PB, Ribeiro CM, Rodrigues ALS, Prediger RD (2015) Effects of agmatine on depressive-like behavior induced by intracerebroventricular administration of 1-methyl-4-phenylpyridinium (MPP(+)). Neurotox Res 28:222–231

    Article  CAS  PubMed  Google Scholar 

  • Muir JK, Lobner D, Monyer H, Choi DW (1996) GABAA receptor activation attenuates excitotoxicity but exacerbates oxygen-glucose deprivation-induced neuronal injury in vitro. J Cereb Blood Flow Metab 16:1211–1218

    Article  CAS  PubMed  Google Scholar 

  • Neis VB, Manosso LM, Moretti M, Freitas AE, Daufenbach J, Rodrigues ALS (2014) Depressive-like behavior induced by tumor necrosis factor-alpha is abolished by agmatine administration. Behav Brain Res 261:336–344

    Article  CAS  PubMed  Google Scholar 

  • Neis VB, Bettio LEB, Moretti M, Rosa PB, Ribeiro CM, Freitas AE, Gonçalves FM, Leal RB, Rodrigues ALS (2016a) Acute agmatine administration, similar to ketamine, reverses depressive-like behavior induced by chronic unpredictable stress in mice. Pharmacol Biochem Behav 150-151:108–114

    Article  CAS  PubMed  Google Scholar 

  • Neis VB, Moretti M, Bettio LE et al (2016b) Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling. Eur Neuropsychopharmacol 26:959–971

    Article  CAS  PubMed  Google Scholar 

  • Neis VB, Rosa PB, Olescowicz G, Rodrigues ALS (2017) Therapeutic potential of agmatine for CNS disorders. Neurochem Int 108:318–331

    Article  CAS  PubMed  Google Scholar 

  • Neis VB, Bettio LB, Moretti M, Rosa PB, Olescowicz G, Fraga DB, Gonçalves FM, Freitas AE, Heinrich IA, Lopes MW, Leal RB, Rodrigues ALS (2018) Single administration of agmatine reverses the depressive-like behavior induced by corticosterone in mice: comparison with ketamine and fluoxetine. Pharmacol Biochem Behav 173:44–50

    Article  CAS  PubMed  Google Scholar 

  • O’Leary OF, Felice D, Galimberti S et al (2014) GABAB(1) receptor subunit isoforms differentially regulate stress resilience. Proc Natl Acad Sci U S A 111:15232–15237

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oh DH, Son H, Hwang S, Kim SH (2012) Neuropathological abnormalities of astrocytes, GABAergic neurons, and pyramidal neurons in the dorsolateral prefrontal cortices of patients with major depressive disorder. Eur Neuropsychopharmacol 22:330–338

    Article  CAS  PubMed  Google Scholar 

  • Parker GB, Graham RK (2015) Determinants of treatment-resistant depression: the salience of benzodiazepines. J Nerv Ment Dis 203:659–663

    Article  PubMed  Google Scholar 

  • Patel MRBR, Kardile DP, Naik RA (2011) Agmatine inhibit the tolerance to the anxiolytic effect of diazepam in rats. Int J Pharm Appl Sci:44–51

  • Paxinos G, Franklin KBJ (2004) The mouse brain in stereotaxic coordinates. Elsevier Academic Press, Amsterdam

    Google Scholar 

  • Petty F, Fulton M, Kramer GL, Kram M, Davis LL, Rush AJ (1999) Evidence for the segregation of a major gene for human plasma GABA levels. Mol Psychiatry 4:587–589

    Article  CAS  PubMed  Google Scholar 

  • Pigott HE, Leventhal AM, Alter GS, Boren JJ (2010) Efficacy and effectiveness of antidepressants: current status of research. Psychother Psychosom 79:267–279

    Article  PubMed  Google Scholar 

  • Piletz JE, Aricioglu F, Cheng JT, Fairbanks CA, Gilad VH, Haenisch B, Halaris A, Hong S, Lee JE, Li J, Liu P, Molderings GJ, Rodrigues ALS, Satriano J, Seong GJ, Wilcox G, Wu N, Gilad GM (2013) Agmatine: clinical applications after 100 years in translation. Drug Discov Today 18:880–893

    Article  CAS  PubMed  Google Scholar 

  • Post RM, Ketter TA, Joffe RT, Kramlinger KL (1991) Lack of beneficial effects of l-baclofen in affective disorder. Int Clin Psychopharmacol 6:197–207

    Article  CAS  PubMed  Google Scholar 

  • Price RB, Shungu DC, Mao X, Nestadt P, Kelly C, Collins KA, Murrough JW, Charney DS, Mathew SJ (2009) Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder. Biol Psychiatry 65:792–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren Z, Pribiag H, Jefferson SJ, Shorey M, Fuchs T, Stellwagen D, Luscher B (2016) Bidirectional homeostatic regulation of a depression-related brain state by gamma-aminobutyric acidergic deficits and ketamine treatment. Biol Psychiatry 80:457–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodrigues AL, Rocha JB, Mello CF, Souza DO (1996) Effect of perinatal lead exposure on rat behaviour in open-field and two-way avoidance tasks. Pharmacol Toxicol 79:150–156

    Article  CAS  PubMed  Google Scholar 

  • Rosa PB, Neis VB, Ribeiro CM, Moretti M, Rodrigues ALS (2016) Antidepressant-like effects of ascorbic acid and ketamine involve modulation of GABAA and GABAB receptors. Pharmacol Rep 68:996–1001

    Article  CAS  PubMed  Google Scholar 

  • Sapkota K, Mao Z, Synowicki P, Lieber D, Liu M, Ikezu T, Gautam V, Monaghan DT (2016) GluN2D N-methyl-d-aspartate receptor subunit contribution to the stimulation of brain activity and gamma oscillations by ketamine: implications for schizophrenia. J Pharmacol Exp Ther 356:702–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sigel E, Ernst M (2018) The benzodiazepine binding sites of GABAA receptors. Trends Pharmacol Sci 39:659–671

    Article  CAS  PubMed  Google Scholar 

  • Spijker J, van Straten A, Bockting CL et al (2013) Psychotherapy, antidepressants, and their combination for chronic major depressive disorder: a systematic review. Can J Psychiatr 58:386–392

    Article  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Taksande BG, Kotagale NR, Patel MR, Shelkar GP, Ugale RR, Chopde CT (2010) Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. Eur J Pharmacol 637:89–101

    Article  CAS  PubMed  Google Scholar 

  • Taksande BG, Sharma O, Aglawe MM, Kale MB, Gawande DY, Umekar MJ, Kotagale NR (2017) Acute orexigenic effect of agmatine involves interaction between central alpha2-adrenergic and GABAergic receptors. Biomed Pharmacother 93:939–947

    Article  CAS  PubMed  Google Scholar 

  • Tavares MK, Dos Reis S, Platt N et al (2018) Agmatine potentiates neuroprotective effects of subthreshold concentrations of ketamine via mTOR/S6 kinase signaling pathway. Neurochem Int 118:275–285

    Article  CAS  PubMed  Google Scholar 

  • Vasavada MM, Leaver AM, Espinoza RT, Joshi SH, Njau SN, Woods RP, Narr KL (2016) Structural connectivity and response to ketamine therapy in major depression: a preliminary study. J Affect Disord 190:836–841

    Article  CAS  PubMed  Google Scholar 

  • Wang HY, Kuo ZC, Fu YS, Chen RF, Min MY, Yang HW (2015) GABAB receptor-mediated tonic inhibition regulates the spontaneous firing of locus coeruleus neurons in developing rats and in citalopram-treated rats. J Physiol 593:161–180

    Article  CAS  PubMed  Google Scholar 

  • Wang DS, Penna A, Orser BA (2017) Ketamine increases the function of gamma-aminobutyric acid type A receptors in hippocampal and cortical neurons. Anesthesiology 126:666–677

    Article  CAS  PubMed  Google Scholar 

  • Widman AJ, McMahon LL (2018) Disinhibition of CA1 pyramidal cells by low-dose ketamine and other antagonists with rapid antidepressant efficacy. Proc Natl Acad Sci U S A 115:3007–3016

    Article  CAS  Google Scholar 

  • Workman ER, Niere F, Raab-Graham KF (2013) mTORC1-dependent protein synthesis underlying rapid antidepressant effect requires GABABR signaling. Neuropharmacology 73:192–203

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto T, Nakayama T, Yamaguchi J, Matsuzawa M, Mishina M, Ikeda K, Yamamoto H (2016) Role of the NMDA receptor GluN2D subunit in the expression of ketamine-induced behavioral sensitization and region-specific activation of neuronal nitric oxide synthase. Neurosci Lett 610:48–53

    Article  CAS  PubMed  Google Scholar 

  • Zarate CA, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856–864

    Article  CAS  PubMed  Google Scholar 

  • Zhang T, Du Y, Liu X et al (2019) Study on antidepressant-like effect of protoilludane sesquiterpenoid aromatic esters from Armillaria Mellea. Nat Prod Res:1–4

  • Zheng W, Xiao-Hong L, Xiao-Min Z et al (2019) Adjunctive ketamine and electroconvulsive therapy for major depressive disorder: A meta-analysis of randomized controlled trials. J Affec Dis 250:123–131

  • Zomkowski ADE, Hammes L, Lin J, Calixto JB, Santos ARS, Rodrigues ALS (2002) Agmatine produces antidepressant-like effects in two models of depression in mice. Neuroreport 13:387–391

    Article  CAS  PubMed  Google Scholar 

  • Zomkowski ADE, Rosa AO, Lin J et al (2004) Evidence for serotonin receptor subtypes involvement in agmatine antidepressant like-effect in the mouse forced swimming test. Brain Res 1023:253–263

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) # 449436/2014-4, # 310113/2017-2 and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). ALSR is a CNPq Research Fellow. V.B.N. acknowledges postdoctoral funding from the CNPq (158126/2018-1).

Author information

Authors and Affiliations

  1. Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil

    Vivian Binder Neis, Axel Fogaça Rosado, Gislaine Olescowicz, Morgana Moretti, Priscila Batista Rosa, Nicole Platt & Ana Lúcia S. Rodrigues

Authors
  1. Vivian Binder Neis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Axel Fogaça Rosado
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gislaine Olescowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Morgana Moretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Priscila Batista Rosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nicole Platt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ana Lúcia S. Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

VBN, GO, and ALSR designed the study and wrote the protocol. VBN, MM, PBR, NP, and AFR conducted experiments. VBN, AFR, and PBR analyzed data. MM and PBR provided essential critical analysis of the manuscript. VBN and ALSR wrote the manuscript and managed the literature searches. All authors contributed to the design, acquisition, analysis, and interpretation of data. All authors read and approved the manuscript.

Corresponding author

Correspondence to Vivian Binder Neis.

Ethics declarations

Animals were used according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the protocol and experiments were approved by the Ethical Committee of Animal Research of Federal University of Santa Catarina.

Conflict of interest

The authors declare that they have no conflict of interest.

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

Neis, V.B., Rosado, A.F., Olescowicz, G. et al. The involvement of GABAergic system in the antidepressant-like effect of agmatine. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1931–1939 (2020). https://doi.org/10.1007/s00210-020-01910-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-020-01910-5

Keywords

Search

Navigation