Hostname: page-component-76fb5796d-22dnz Total loading time: 0 Render date: 2024-04-26T05:45:19.030Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of NMDAR antagonists in the tetrabenazine test for antidepressants: comparison with the tail suspension test

Published online by Cambridge University Press:  10 April 2015

Phil Skolnick ,
Tomasz Kos ,
Janusz Czekaj  and
Piotr Popik
Phil Skolnick
Affiliation:
Division of Pharmacotherapies & Medical Consequences of Drug Abuse, NIDA, NIH, Bethesda, MD, USA
Tomasz Kos
Affiliation:
Behavioral Neuroscience and Drug Development Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
Janusz Czekaj
Affiliation:
Faculty of Health Sciences, Collegium Medicum, Jagiellonian University, Kraków, Poland
Piotr Popik*
Affiliation:
Behavioral Neuroscience and Drug Development Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland Faculty of Health Sciences, Collegium Medicum, Jagiellonian University, Kraków, Poland
*
Piotr Popik, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland. Tel: +48+12 6623375; Fax: +48+12 6374500; E-mail: nfpopik@cyf-kr.edu.pl
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine, produces rapid and enduring antidepressant effect in patients with treatment-resistant depression. Similar dramatic effects have not been observed in clinical trials with other NMDAR antagonists indicating ketamine may possess unique pharmacological properties. Tetrabenazine induces ptosis (a drooping of the eyelids), and the reversal of this effect, attributed to a sympathomimetic action, has been used to detect first-generation antidepressants, as well as ketamine. Because the actions of other NMDAR antagonists have not been reported in this measure, we examined whether reversal of tetrabenazine-induced ptosis was unique to ketamine, or a class effect of NMDAR antagonists.

Methods

The effects of ketamine and other NMDAR antagonists to reverse tetrabenazine-induced ptosis were examined and compared with their antidepressant-like effects in the tail suspension test (TST) in mice.

Results

All the NMDAR antagonists tested produced a partial reversal of tetrabenazine-induced ptosis and, as expected, reduced immobility in the TST. Ketamine, memantine, MK-801 and AZD6765 were all about half as potent in reversing tetrabenazine-induced ptosis compared to reducing immobility in the TST, while an NR2B antagonist (Ro 25-6981) and a glycine partial agonist (ACPC) were equipotent in both tests.

Conclusion

The ability to reverse tetrabenazine-induced ptosis is a class effect of NMDAR antagonists. These findings are consistent with the hypothesis that the inability of memantine, AZD6765 (lanicemine) and MK-0657 to reproduce the rapid and robust antidepressant effects of ketamine in the clinic result from insufficient dosing rather than a difference in mechanism of action among these NMDAR antagonists.

Keywords

antidepressantNMDAR antagonistptosistail suspension testtetrabenazine
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 4 , August 2015 , pp. 228 - 234
Check for updates
Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Murrough, JW. Ketamine as a novel antidepressant: from synapse to behavior. Clin Pharmacol Ther 2012;91:303–309.CrossRefGoogle ScholarPubMed
2.Martin, D, Lodge, D. Ketamine acts as a non-competitive N-methyl-d-aspartate antagonist on frog spinal cord in vitro. Neuropharmacology 1985;24:999–1003.CrossRefGoogle ScholarPubMed
3.Mealing, GA, Lanthorn, TH, Murray, CLet al. Differences in degree of trapping of low-affinity uncompetitive N-methyl-d-aspartic acid receptor antagonists with similar kinetics of block. J Pharmacol Exp Ther 1999;288:204–210.Google ScholarPubMed
4.Zarate, CA, Singh, JB, Quiroz, JAet al. A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry 2006;163:153–155.CrossRefGoogle ScholarPubMed
5.Zarate, CA, Mathews, D, Ibrahim, Let al. A randomized trial of a low-trapping nonselective N-methyl-d-aspartate channel blocker in major depression. Biol Psychiatry 2013;74:257–264.CrossRefGoogle ScholarPubMed
6.Sanacora, G, Smith, MA, Pathak, Set al. Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects. Mol Psychiatry 2014;19:978–985.CrossRefGoogle ScholarPubMed
7.Lord, B, Wintmolders, C, Langlois, Xet al. Comparison of the ex vivo receptor occupancy profile of ketamine to several NMDA receptor antagonists in mouse hippocampus. Eur J Pharmacol 2013;715:21–25.CrossRefGoogle ScholarPubMed
8.Porsolt, RD, Pichon, LE, Jalfre, M. Depression: a new animal model sensitive to antidepressant treatments. Nature 1977;266:730–732.CrossRefGoogle ScholarPubMed
9.Steru, L, Chermat, R, Thierry, B, Simon, P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 1985;85:367–370.CrossRefGoogle Scholar
10.Pilc, A, Wieronska, JM, Skolnick, P. Glutamate-based antidepressants: preclinical psychopharmacology. Biol Psychiatry 2013;73:1125–1132.CrossRefGoogle ScholarPubMed
11.Borsini, F, Meli, A. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology 1988;94:147–160.CrossRefGoogle Scholar
12.Cryan, JF, Valentino, RJ, Lucki, I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci Biobehav Rev 2005;29:547–569.CrossRefGoogle ScholarPubMed
13.Sofia, RD, Harakal, JJ. Evaluation of ketamine HCl for anti-depressant activity. Arch Inter Pharmacodyn Ther 1975;214:68–74.Google ScholarPubMed
14.Miletich, DJ, Ivankovic, AD, Albrecht, RFet al. The effect of ketamine on catecholamine metabolism in the isolated perfused rat heart. Anesthesiology 1973;39:271–277.CrossRefGoogle ScholarPubMed
15.Steru, L, Chermat, R, Thierry, Bet al. The automated tail suspension test: a computerized device which differentiates psychotropic drugs. Prog Neuropsychopharmacol Biol Psychiatry 1987;11:659–671.CrossRefGoogle Scholar
16.Bechtholt, AJ, Smith, K, John, CSet al. CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy. Psychopharmacology 2011;215:689–695.CrossRefGoogle Scholar
17.Kos, T, Popik, P, Pietraszek, Met al. Effect of 5-HT3 receptor antagonist MDL 72222 on behaviors induced by ketamine in rats and mice. Eur Neuropsychopharmacol 2006;16:297–310.CrossRefGoogle ScholarPubMed
18.Kos, T, Popik, P. A comparison of the predictive therapeutic and undesired side-effects of NMDA receptor antagonist, memantine in mice. Behav Pharmacol 2005;16:155–161.CrossRefGoogle ScholarPubMed
19.Eckeli, AL, Dach, F, Rodrigues, ALS. Acute treatments with GMP produce antidepressant-like effects in mice. NeuroReport 2000;11:1839–1843.CrossRefGoogle ScholarPubMed
20.Kiselycznyk, CL, Svenningsson, P, Delpire, E, Holmes, A. Genetic, pharmacological and lesion analyses reveal a selective role for corticohippocampal GLUN2B in a novel repeated swim stress paradigm. Neuroscience 2011;193:259–268.CrossRefGoogle Scholar
21.Trullas, R, Folio, T, Young, Aet al. 1-Aminocyclopropanecarboxylates exhibit antidepressant and anxiolytic actions in animal models. Eur J Pharmacol 1991;203:379–385.CrossRefGoogle ScholarPubMed
22.Sanchez-Mateo, CC, Bonkanka, CX, Prado, B, Rabanal, RM. Antidepressant activity of some Hypericum reflexum L. fil. extracts in the forced swimming test in mice. J Ethnopharmacol 2007;112:115–121.CrossRefGoogle ScholarPubMed
23.Popik, P, Kos, T, Sowa-Kucma, M, Nowak, G. Lack of persistent effects of ketamine in rodent models of depression. Psychopharmacology 2008;198:421–430.CrossRefGoogle ScholarPubMed
24.Jernigan, CS, Goswami, DB, Austin, MCet al. The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:1774–1779.CrossRefGoogle ScholarPubMed
25.Newton, SS, Fournier, NM, Duman, RS. Vascular growth factors in neuropsychiatry. Cell Mol Life Sci 2013;70:1739–1752.CrossRefGoogle ScholarPubMed
26.Murck, H. Ketamine, magnesium and major depression – from pharmacology to pathophysiology and back. J Psychiat Res 2013;47:955–965.CrossRefGoogle ScholarPubMed
27.Lindholm, JS, Autio, H, Vesa, Let al. The antidepressant-like effects of glutamatergic drugs ketamine and AMPA receptor potentiator LY 451646 are preserved in bdnf(+/-) heterozygous null mice. Neuropharmacology 2012;62:391–397.CrossRefGoogle ScholarPubMed
28.Autry, AE, Adachi, M, Nosyreva, Eet al. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 2011;475:91–95.CrossRefGoogle ScholarPubMed
29.Dybala, M, Siwek, A, Poleszak, Eet al. Lack of NMDA-AMPA interaction in antidepressant-like effect of CGP 37849, an antagonist of NMDA receptor, in the forced swim test. J Neural Transm 2008;115:1519–1520.CrossRefGoogle ScholarPubMed
30.Maeng, S, Zarate, CA Jr., DU, Jet al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 2008;63:349–352.CrossRefGoogle ScholarPubMed
31.Wolak, M, Siwek, A, Szewczyk, Bet al. Involvement of NMDA and AMPA receptors in the antidepressant-like activity of antidepressant drugs in the forced swim test. Pharmacological Reports 2013;65:991–997.CrossRefGoogle ScholarPubMed
32.Papp, M, Moryl, E. Antidepressant activity of non-competitive NMDA antagonists in a chronic mild stress model of depression. Eur J Pharmacol 1994;263:1–7.CrossRefGoogle Scholar
33.Li, N, Liu, RJ, Dwyer, JMet al. Glutamate N-methyl-d-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 2011;69:754–761.CrossRefGoogle ScholarPubMed
34.Ibrahim, L, Diaz, GN, Jolkovsky, Let al. A Randomized, placebo-controlled, crossover pilot trial of the oral selective NR2B antagonist MK-0657 in patients with treatment-resistant major depressive disorder. J Clin Psychopharmacol 2012;32:551–557.CrossRefGoogle ScholarPubMed
35.Virtue, RW, Alanis, JM, Mori, Met al. An anesthetic agent: 2-orthochlorophenyl, 2-methylamino cyclohexanone HCl (CI-581). Anesthesiology 1967;28:823–833.CrossRefGoogle ScholarPubMed
36.Willner, P. The validity of animal models of depression. Psychopharmacology 1984;83:1–16.CrossRefGoogle ScholarPubMed
37.Clineschmidt, BV, Martin, GE, Bunting, PR, Papp, NL. Central symphatomimetic activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympatomimetic and apparent anxiolytic properties. Drug Dev Res 1982;2:135–145.CrossRefGoogle Scholar
38.Wong, EHF, Kemp, JA, Priestley, Tet al. The anticonvulsant MK-801 is a potent N-methyl-d-aspartate antagonist. Proc Natl Acad Sci USA 1986;83:7104–7108.CrossRefGoogle ScholarPubMed
39.Lewis, SJ, Barres, C, Jacob, HJet al. Cardiovascular effects of the N-methyl-d-aspartate receptor antagonist MK-801 in conscious rats. Hypertension 1989;13:759–765.CrossRefGoogle ScholarPubMed
40.Forest Laboratories. NAMENDA (memantine hydrochloride) PDR, 2013. Available at http://www.frx.com/pi/namenda_pi.pdf, accessed on March 2015.Google Scholar
41.Reus, GZ, Abelaira, H, Stringari, Ret al. Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats. Metab Brain Dis 2012;27:175–182.CrossRefGoogle ScholarPubMed
42.Rogoz, Z, Skuza, G, Maj, J, Danysz, W. Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats. Neuropharmacology 2002;42:1024–1030.CrossRefGoogle ScholarPubMed
43.Moryl, E, Danysz, W, Quack, G. Potential antidepressive properties of amantadine, memantine and bifemelane. Pharmacol Toxicol 1993;72:394–397.CrossRefGoogle ScholarPubMed
44.Parsons, CG, Danysz, W, Quack, G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist – a review of preclinical data. Neuropharmacology 1999;38:735–767.CrossRefGoogle ScholarPubMed
45.Addy, C, Assaid, C, Hreniuk, Det al. Single-dose administration of MK-0657, an NR2B-selective NMDA antagonist, does not result in clinically meaningful improvement in motor function in patients with moderate Parkinson’s disease. J Clin Pharmacol 2009;49:856–864.CrossRefGoogle Scholar
46.Schatzberg, AF. A word to the wise about ketamine. Am J Psychiatry 2014;171:262–264.CrossRefGoogle Scholar
47.Mcgirr, A, Berlim, MT, Bond, DJet al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med 2014:1–12.Google ScholarPubMed
48.Leppik, IE, Marienau, K, Graves, NM, Rask, CA. MK-801 for epilepsy: a pilot study. Neurology 1988;38(Suppl. 1):405.Google Scholar
49.Riederer, P, Lange, KW, Kornhuber, J, Danielczyk, W. Pharmacotoxic psychosis after memantine in Parkinson’s disease. Lancet 1991;338:1022–1023.CrossRefGoogle ScholarPubMed
50.Luckenbaugh, DA, Niciu, MJ, Ionescu, DFet al. Do the dissociative side effects of ketamine mediate its antidepressant effects? J Affect Disord 2014;159:56–61.CrossRefGoogle ScholarPubMed