Abstract
Rationale
The antidepressant action of acute nicotine administration in clinical and animal studies is well recognized. But the underlying mechanism for this effect has not been carefully discovered.
Objectives
We attempted to evaluate the possible role of N-Methyl-d-aspartate (NMDA) receptors in the antidepressant-like effect of nicotine.
Methods
After the assessment of locomotor activity in the open-field test, forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant-like effect of nicotine in mice. We performed intraperitoneal administration of nicotine at different doses and periods before the tests. To assess the possible involvement of NMDA receptors, non-effective doses of NMDA antagonists and an NMDA agonist were obtained and were administered simultaneously with the non-effective and effective doses of nicotine, respectively.
Results
Nicotine (0.2 mg/kg, 30 min before FST/TST) significantly reduced the immobility time of mice similar to fluoxetine (20 mg/kg). Nicotine did not affect the locomotor behavior of mice in open-field test. Co-administration of non-effective doses of NMDA receptor antagonists, ketamine (1 or 0.3 mg/kg), MK-801 (0.05 or 0.005 mg/kg), and magnesium sulfate (10 or 5 mg/kg) with nicotine (0.1 or 0.03 mg/kg) had remarkable synergistic antidepressant effect in both FST and TST. Also, non-effective NMDA (75 or 30 mg/kg) reversed the anti-immobility effect of nicotine (0.2 mg/kg) on mouse FST and TST.
Conclusions
Our study has for the first time confirmed that the antidepressant-like effect of nicotine on mice is NMDA-mediated, and nicotine presumably exerts this effect by antagonizing the glutamatergic NMDA receptors.
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References
Aceto MD, Awaya H, Martin BR, May EL (1983) Antinociceptive action of nicotine and its methiodide derivatives in mice and rats. Br J Pharmacol 79:869–876
Aizenman E, Tang L-H, Reynolds IJ (1991) Effects of nicotinic agonists on the NMDA receptor. Brain Res 551:355–357
Andreasen JT, Redrobe JP (2009) Antidepressant-like effects of nicotine and mecamylamine in the mouse forced swim and tail suspension tests: role of strain, test and sex. Behav Pharmacol 20:286–295
Andreasen J, Olsen G, Wiborg O, Redrobe J (2009) Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests. J Psychopharmacol 23:797–804
Aramakis VB, Metherate R (1998) Nicotine selectively enhances NMDA receptor-mediated synaptic transmission during postnatal development in sensory neocortex. J Neurosci 18:8485–8495
Arroll B, Macgillivray S, Ogston S, Reid I, Sullivan F, Williams B, Crombie I (2005) Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis. Ann Fam Med 3:449–456
Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng P-f, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475:91–95
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
Berrendero F, Plaza-Zabala A, Galeote L, Flores Á, Bura SA, Kieffer BL, Maldonado R (2012) Influence of δ-opioid receptors in the behavioral effects of nicotine. Neuropsychopharmacology 37:2332–2344
Bourin M, Chenu F, Ripoll N, David DJP (2005) A proposal of decision tree to screen putative antidepressants using forced swim and tail suspension tests. Behav Brain Res 164:266–269
Castagné V, Moser P, Roux S, Porsolt RD (2011) Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Curr Protoc Neurosci 55:11–18.10
Cryan JF, Markou A, Lucki I (2002) Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 23:238–245
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
Cunha MP, Pazini FL, Ludka FK, Rosa JM, Oliveira Á, Budni J, Ramos-Hryb AB, Lieberknecht V, Bettio LEB, Martín-de-Saavedra MD (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: 1-17
Damaj M, Glassco W, Dukat M, Martin B (1999) Pharmacological characterization of nicotine-induced seizures in mice. J Pharmacol Exp Ther 291:1284–1291
Djurić VJ, Dunn E, Overstreet DH, Dragomir A, Steiner M (1999) Antidepressant effect of ingested nicotine in female rats of Flinders resistant and sensitive lines. Physiol Behav 67:533–537
Ferguson SM, Brodkin JD, Lloyd GK, Menzaghi F (2000) Antidepressant-like effects of the subtype-selective nicotinic acetylcholine receptor agonist, SIB-1508Y, in the learned helplessness rat model of depression. Psychopharmacology 152:295–303
Fromm L, Heath DL, Vink R, Nimmo AJ (2004) Magnesium attenuates post-traumatic depression/anxiety following diffuse traumatic brain injury in rats. J Am Coll Nutr 23:529S–533S
Ghasemi M, Raza M, Dehpour A (2009) NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test. J Psychopharmacol
Ghasemi M, Raza M, Dehpour A (2010) NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test. J Psychopharmacol 24:585–594
Glassman AH (1993) Cigarette smoking: implications for psychiatric illness. Am J Psychiatry
Glassman AH, Covey LS, Stetner F, Rivelli S (2001) Smoking cessation and the course of major depression: a follow-up study. Lancet 357:1929–1932
Gómez M, Martínez-Mota L, Estrada-Camarena E, Fernández-Guasti A (2014) Influence of the brain sexual differentiation process on despair and antidepressant-like effect of fluoxetine in the rat forced swim test. Neuroscience 261:11–22
Haj-Mirzaian A, Hamzeh N, Javadi-Paydar M, Abdollahzadeh Estakhri MR, Dehpour AR (2013) Resistance to depression through interference of opioid and nitrergic systems in bile-duct ligated mice. Eur J Pharmacol 708:38–43
Haj-Mirzaian A, Ostadhadi S, Kordjazy N, Dehpour AR, Mehr SE (2014) Opioid/NMDA receptors blockade reverses the depressant-like behavior of foot shock stress in the mouse forced swimming test. Eur J Pharmacol
Haj-Mirzaian A, Amiri S, Kordjazy N, Rahimi-Balaei M, Haj-Mirzaian A, Marzban H, Dehpour AR, Mehr SE (2015) Blockade of NMDA receptors reverses the depressant, but not anxiogenic effect of adolescence social isolation in mice. Eur J Pharmacol
Hasanein P, Parviz M, Keshavarz M, Javanmardi K, Allahtavakoli M, Ghaseminejad M (2007) Modulation of cholestasis-induced antinociception in rats by two NMDA receptor antagonists: MK-801 and magnesium sulfate. Eur J Pharmacol 554:123–127
Hayase T (2011) Differential effects of TRPV1 receptor ligands against nicotine-induced depression-like behaviors. BMC Pharmacol 11:6
Iniguez SD, Warren BL, Parise EM, Alcantara LF, Schuh B, Maffeo ML, Manojlovic Z, Bolanos-Guzmán CA (2009) Nicotine exposure during adolescence induces a depression-like state in adulthood. Neuropsychopharmacology 34:1609–1624
Jha P (2009) Avoidable global cancer deaths and total deaths from smoking. Nat Rev Cancer 9:655–664
Ji S, Mataki C, Yamada S, Nankai M, Toru M (1998) Antidepressantlike effects of chronic nicotine on learned helplessness paradigm in rats. Biol Psychiatry 43:389–391
Kaymak C, Yilmaz E, Basar H, Ozcakir S, Apan A, Batislam E (2007) Use of the NMDA antagonist magnesium sulfate during monitored anesthesia care for shockwave lithotripsy. J Endourol 21:145–150
Levin ED, Simon BB (1998) Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology 138:217–230
Maj J, Rogóż Z, Skuza G, Sowińska H (1992) Effects of MK-801 and antidepressant drugs in the forced swimming test in rats. Eur Neuropsychopharmacol 2:37–41
Manji HK, Drevets WC, Charney DS (2001) The cellular neurobiology of depression. Nat Med 7
Mannucci C, Tedesco M, Bellomo M, Caputi AP, Calapai G (2006) Long-term effects of nicotine on the forced swimming test in mice: an experimental model for the study of depression caused by smoke. Neurochem Int 49:481–486
Mantovani M, Pértile R, Calixto JB, Santos AR, Rodrigues ALS (2003a) Melatonin exerts an antidepressant-like effect in the tail suspension test in mice: evidence for involvement of < i > N</i > -methyl-d-aspartate receptors and the l-arginine-nitric oxide pathway. Neurosci Lett 343:1–4
Mantovani M, Pértile R, Calixto JB, Santos ARS, Rodrigues ALS (2003b) Melatonin exerts an antidepressant-like effect in the tail suspension test in mice: evidence for involvement of N-methyl-D-aspartate receptors and the L-arginine-nitric oxide pathway. Neurosci Lett 343:1–4
Mathalon DH, Ahn K-H, Perry Jr EB, Cho H-S, Roach BJ, Blais RK, Bhakta S, Ranganathan M, Ford JM, D’Souza DC (2014) Effects of nicotine on the neurophysiological and behavioral effects of ketamine in humans. Front Psychiatry 5
Mattila M, Ahtee L, Saarnivaara L (1968) The analgesic and sedative effects of nicotine in white mice, rabbits and golden hamsters Ann Med Exp Biol Fenn: 78
McClernon FJ, Hiott FB, Westman EC, Rose JE, Levin ED (2006) Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial. Psychopharmacology 189:125–133
Mineur YS, Picciotto MR (2010) Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis. Trends Pharmacol Sci 31:580–586
O’Leary OF, Bechtholt AJ, Crowley JJ, Hill TE, Page ME, Lucki I (2007) Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test. Psychopharmacology 192:357–371
O'dell T, Christensen B (1988) Mecamylamine is a selective non-competitive antagonist of N-methyl-D-aspartate-and aspartate-induced currents in horizontal cells dissociated from the catfish retina. Neurosci Lett 94:93–98
Owolabi RA, Akanmu MA, Adeyemi OI (2014) Effects of ketamine and < i > N</i > -methyl-d-aspartate on fluoxetine-induced antidepressant-related behavior using the forced swimming test. Neurosci Lett 566:172–176
Pałucha-Poniewiera A, Pilc A (2012) Involvement of mGlu5 and NMDA receptors in the antidepressant-like effect of acamprosate in the tail suspension test. Prog Neuro-Psychopharmacol Biol Psychiatry 39:102–106
Perrault GH, Morel E, Zivkovic B, Sanger DJ (1992) Activity of litoxetine and other serotonin uptake inhibitors in the tail suspension test in mice. Pharmacol Biochem Behav 42:45–47
Picciotto MR, Brunzell DH, Caldarone BJ (2002) Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport 13:1097–1106
Poleszak E, Wlaz P, Kêdzierska E, Radziwon-Zaleska M, Pilc A, Fidecka S, Nowak G (2005a) Effects of acute and chronic treatment with magnesium in the forced swim test in rats. Pharmacol Rep 57:654–658
Poleszak E, Wlaź P, Szewczyk B, Kędzierska E, Wyska E, Librowski T, Szymura-Oleksiak J, Fidecka S, Pilc A, Nowak G (2005b) Enhancement of antidepressant-like activity by joint administration of imipramine and magnesium in the forced swim test: behavioral and pharmacokinetic studies in mice. Pharmacol Biochem Behav 81:524–529
Poleszak E, Wlaz P, Kêdzierska E, Nieoczym D, Wyska E, Szymura-Oleksiak J, Fidecka S, Radziwon-Zaleska M, Nowak G (2006) Immobility stress induces depression-like behavior in the forced swim test in mice: effect of magnesium and imipramine. Pharmacol Rep 58:746
Poleszak E, Wlaź P, Kędzierska E, Nieoczym D, Wróbel A, Fidecka S, Pilc A, Nowak G (2007) NMDA/glutamate mechanism of antidepressant-like action of magnesium in forced swim test in mice. Pharmacol Biochem Behav 88:158–164
Popik P, Kozela E, Krawczyk M (2003) Nicotine and nicotinic receptor antagonists potentiate the antidepressant‐like effects of imipramine and citalopram. Br J Pharmacol 139:1196–1202
Porsolt R, Bertin A, Jalfre M (1977a) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327
Porsolt RD, Le Pichon M, Jalfre M (1977b) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732
Ramoa A, Alkondon M, Aracava Y, Irons J, Lunt G, Deshpande S, Wonnacott S, Aronstam R, Albuquerque E (1990) The anticonvulsant MK-801 interacts with peripheral and central nicotinic acetylcholine receptor ion channels. J Pharmacol Exp Ther 254:71–82
Roni MA, Rahman S (2014) The effects of lobeline on nicotine withdrawal-induced depression-like behavior in mice. Psychopharmacology: 1-10
Sadaghiani MS, Javadi-Paydar M, Gharedaghi MH, Fard YY, Dehpour AR (2011) Antidepressant-like effect of pioglitazone in the forced swimming test in mice: the role of PPAR-gamma receptor and nitric oxide pathway. Behav Brain Res 224:336–343
SalÃn-Pascual RJ, Rosas M, Jimenez-Genchi A, Rivera-Meza BL (1996) Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression. J Clin Psychiatry
Salehi-Sadaghiani M, Javadi-Paydar M, Gharedaghi MH, Zandieh A, Heydarpour P, Yousefzadeh-fard Y, Dehpour AR (2012) NMDA receptor involvement in antidepressant-like effect of pioglitazone in the forced swimming test in mice. Psychopharmacology 223:345–355
Salín-Pascual RJ (2002) Nicotine antidepressant effects as a predictor of response to desimipramine or fluoxetine in non-smoking major depressed patients. Salud Mental 25:16–20
Salín-Pascual RJ, Drucker-Colín R (1998) A novel effect of nicotine on mood and sleep in major depression. Neuroreport 9:57–60
Santos T, Baungratz MM, Haskel SP, de Lima DD, da Cruz JN, Magro D, da Cruz J (2011) Behavioral interactions of simvastatin and fluoxetine in tests of anxiety and depression. Neuropsychiatr Dis Treat 8:413–422
Schnoll RA, Leone FT, Hitsman B (2013) Symptoms of depression and smoking behaviors following treatment with transdermal nicotine patch. J Addict Dis 32:46–52
Shim I, Kim H-T, Kim Y-H, Chun B-G, Hahm D-H, Lee EH, Kim SE, Lee H-J (2002) Role of nitric oxide synthase inhibitors and NMDA receptor antagonist in nicotine-induced behavioral sensitization in the rat. Eur J Pharmacol 443:119–124
Skolnick P, Popik P, Trullas R (2009) Glutamate-based antidepressants: 20 years on. Trends Pharmacol Sci 30:563–569
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
Suemaru K, Yasuda K, Cui R, Li B, Umeda K, Amano M, Mitsuhashi H, Takeuchi N, Inoue T, Gomita Y (2006) Antidepressant-like action of nicotine in forced swimming test and brain serotonin in mice. Physiol Behav 88:545–549
Szasz BK, Mike A, Karoly R, Gerevich Z, Illes P, Vizi ES, Kiss JP (2007) Direct inhibitory effect of fluoxetine on N-methyl-D-aspartate receptors in the central nervous system. Biol Psychiatry 62:1303–1309
Tizabi Y, Overstreet DH, Rezvani AH, Louis VA, Clark E Jr, Janowsky DS, Kling MA (1999) Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology 142:193–199
Tokita K, Yamaji T, Hashimoto K (2012) Roles of glutamate signaling in preclinical and/or mechanistic models of depression. Pharmacol Biochem Behav 100:688–704
Trullas R, Skolnick P (1990) Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol 185:1–10
Umathe SN, Manna SS, Jain NS (2011) Involvement of endocannabinoids in antidepressant and anti-compulsive effect of fluoxetine in mice. Behav Brain Res 223:125–134
Vazquez-Palacios G, Bonilla-Jaime H, Velazquez-Moctezuma J (2004) Antidepressant-like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with flouxetine. Pharmacol Biochem Behav 78:165–169
Vázquez-Palacios G, Bonilla-Jaime H, Velázquez-Moctezuma J (2005) Antidepressant effects of nicotine and fluoxetine in an animal model of depression induced by neonatal treatment with clomipramine. Prog Neuro-Psychopharmacol Biol Psychiatry 29:39–46
Vieyra-Reyes P, Mineur YS, Picciotto MR, Túnez I, Vidaltamayo R, Drucker-Colín R (2008) Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression. Brain Res Bull 77:13–18
Wolak M, Siwek A, Szewczyk B, Poleszak E, Bystrowska B, Moniczewski A, Rutkowska A, Młyniec K, Nowak G (2014) Evaluation of the role of NMDA receptor function in antidepressant-like activity. A new study with citalopram and fluoxetine in the forced swim test in mice. Pharmacol Rep
X-t G, Shao F, **e X, Chen L, Wang W (2014) Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine. Pharmacol Biochem Behav 124:361–366
Yildiz F, Erden BF, Ulak G, Utkan T, Gacar N (2000) Antidepressant-like effect of 7-nitroindazole in the forced swimming test in rats. Psychopharmacology 149:41–44
Zarrindast M-R, Sadegh M, Shafaghi B (1996) Effects of nicotine on memory retrieval in mice. Eur J Pharmacol 295:1–6
Zarrindast MR, Aghamohammadi-Sereshki A, Rezayof A, Rostami P (2012) Nicotine-induced anxiogenic-like behaviours of rats in the elevated plus-maze: possible role of NMDA receptors of the central amygdala. J Psychopharmacol 26:555–563
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This study was funded by research operating grants from the Experimental Medicine Research Center, Tehran University of Medical Sciences.
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Haj-Mirzaian, A., Kordjazy, N., Haj-Mirzaian, A. et al. Evidence for the involvement of NMDA receptors in the antidepressant-like effect of nicotine in mouse forced swimming and tail suspension tests. Psychopharmacology 232, 3551–3561 (2015). https://doi.org/10.1007/s00213-015-4004-0
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DOI: https://doi.org/10.1007/s00213-015-4004-0