Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
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Ketamine-Induced Behavioral Effects Across Different Sub-Anesthetic Dose Ranges in Adolescent and Adult Mice

다양한 마취하 용량에서 케타민에 의해 유발된 청소년기 및 성체 마우스의 행동학적 변화

  • Choi, Hyung Jun (Department of Mental Health Research, National Center for Mental Health) ;
  • Im, Soo Jung (Department of Mental Health Research, National Center for Mental Health) ;
  • Park, Hae Ri (Department of Mental Health Research, National Center for Mental Health) ;
  • Lee, Seong Mi (Department of Mental Health Research, National Center for Mental Health) ;
  • Kim, Chul-Eung (Mental Health Research Institute, National Center for Mental Health) ;
  • Ryu, Seunghyong (Department of Psychiatry, Chonnam National University Medical School)
  • 최형준 (국립정신건강센터 정신보건연구과) ;
  • 임수정 (국립정신건강센터 정신보건연구과) ;
  • 박해리 (국립정신건강센터 정신보건연구과) ;
  • 이성미 (국립정신건강센터 정신보건연구과) ;
  • 김철응 (국립정신건강센터 정신건강연구소) ;
  • 류승형 (전남대학교 의과대학 정신건강의학교실)
  • Received : 2019.12.09
  • Accepted : 2020.03.20
  • Published : 2020.04.30
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Abstract

Objectives Ketamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigate the behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice. Methods In each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly divided into 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive 3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT) and forced swim test (FST), respectively. Results In case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman's rho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobility in the FST (Spearman's rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher compared to the saline-treated mice (Dunnett's post-hoc test, p = 0.012). Conclusions We found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobility in mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.

Keywords

References

  1. Schmid RL, Sandler AN, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain 1999;82:111-125. https://doi.org/10.1016/S0304-3959(99)00044-5
  2. Petrenko AB, Yamakura T, Baba H, Shimoji K. The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review. Anesth Analg 2003;97:1108-1116.
  3. Hirota K, Lambert DG. Ketamine: its mechanism(s) of action and unusual clinical uses. Br J Anaesth 1996;77:441-444. https://doi.org/10.1093/bja/77.4.441
  4. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000;47:351-354. https://doi.org/10.1016/S0006-3223(99)00230-9
  5. Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, et al. Antidepressant efficacy of ketamine in treatmentresistant major depression: a two-site randomized controlled trial. Am J Psychiatry 2013;170:1134-1142. https://doi.org/10.1176/appi.ajp.2013.13030392
  6. Phillips JL, Norris S, Talbot J, Birmingham M, Hatchard T, Ortiz A, et al. Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: a randomized controlled trial. Am J Psychiatry 2019;176:401-409. https://doi.org/10.1176/appi.ajp.2018.18070834
  7. Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63:856-864. https://doi.org/10.1001/archpsyc.63.8.856
  8. Kim Y, Shin C. Rapid-acting antidepressant effect of ketamine and its clinical application. J Korean Neuropsychiatr Assoc 2018;57:108-118. https://doi.org/10.4306/jknpa.2018.57.2.108
  9. Scheuing L, Chiu CT, Liao HM, Chuang DM. Antidepressant mechanism of ketamine: perspective from preclinical studies. Front Neurosci 2015;9:249.
  10. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994;51:199-214. https://doi.org/10.1001/archpsyc.1994.03950030035004
  11. Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 2001;25:455-467. https://doi.org/10.1016/S0893-133X(01)00243-3
  12. Cheon JS. Experimental models of schizophrenia. Korean J Biol Psychiatry 1999;6:153-160.
  13. Woo Y, Lee S, Jeong J, Park SK. Use of behavioral analysis in animal models for schizophrenia research. Korean J Schizophr Res 2014;17:12-26. https://doi.org/10.16946/kjsr.2014.17.1.12
  14. Moghaddam B, Adams B, Verma A, Daly D. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci 1997;17:2921-2927. https://doi.org/10.1523/jneurosci.17-08-02921.1997
  15. Homayoun H, Moghaddam B. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 2007;27:11496-11500. https://doi.org/10.1523/JNEUROSCI.2213-07.2007
  16. Chowdhury GM, Zhang J, Thomas M, Banasr M, Ma X, Pittman B, et al. Transiently increased glutamate cycling in rat PFC is associated with rapid onset of antidepressant-like effects. Mol Psychiatry 2017;22:120-126. https://doi.org/10.1038/mp.2016.34
  17. Kim K, Park K, Jang H, Lee Y, Park S. Attunement disorder: a disorder of brain connectivity. Korean J Biol Psychiatry 2013;20:136-143.
  18. Cohen SM, Tsien RW, Goff DC, Halassa MM. The impact of NMDA receptor hypofunction on GABAergic neurons in the pathophysiology of schizophrenia. Schizophr Res 2015;167:98-107. https://doi.org/10.1016/j.schres.2014.12.026
  19. Yankelevitch-Yahav R, Franko M, Huly A, Doron R. The forced swim test as a model of depressive-like behavior. J Vis Exp 2015:52587.
  20. da Silva FC, do Carmo de Oliveira Cito M, da Silva MI, Moura BA, de Aquino Neto MR, Feitosa ML, et al. Behavioral alterations and pro-oxidant effect of a single ketamine administration to mice. Brain Res Bull 2010;83:9-15. https://doi.org/10.1016/j.brainresbull.2010.05.011
  21. Garcia LS, Comim CM, Valvassori SS, Reus GZ, Barbosa LM, Andreazza AC, et al. Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:140-144. https://doi.org/10.1016/j.pnpbp.2007.07.027
  22. Chindo BA, Adzu B, Yahaya TA, Gamaniel KS. Ketamine-enhanced immobility in forced swim test: a possible animal model for the negative symptoms of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2012;38:310-316. https://doi.org/10.1016/j.pnpbp.2012.04.018
  23. Rocha A, Hart N, Trujillo KA. Differences between adolescents and adults in the acute effects of PCP and ketamine and in sensitization following intermittent administration. Pharmacol Biochem Behav 2017;157:24-34. https://doi.org/10.1016/j.pbb.2017.04.007
  24. Semple BD, Blomgren K, Gimlin K, Ferriero DM, Noble-Haeusslein LJ. Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol 2013;106-107:1-16. https://doi.org/10.1016/j.pneurobio.2013.04.001
  25. Browne CA, Lucki I. Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants. Front Pharmacol 2013;4:161. https://doi.org/10.3389/fphar.2013.00161
  26. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008;22:659-661. https://doi.org/10.1096/fj.07-9574lsf
  27. Thelen C, Sens J, Mauch J, Pandit R, Pitychoutis PM. Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice. Behav Brain Res 2016;312:305-312. https://doi.org/10.1016/j.bbr.2016.06.041
  28. Sestakova N, Puzserova A, Kluknavsky M, Bernatova I. Determination of motor activity and anxiety-related behaviour in rodents: methodological aspects and role of nitric oxide. Interdiscip Toxicol 2013;6:126-135. https://doi.org/10.2478/intox-2013-0020
  29. Park JW, Kim DW, Shin KM, Noh JS. Dissociated antidepressant and analgesic effects of intravenous ketamine in patients with chronic pain. Korean J Psychopharmacol 2014;25:192-199.
  30. Noda Y, Yamada K, Furukawa H, Nabeshima T. Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine: a new model of schizophrenia. Br J Pharmacol 1995;116:2531-2537. https://doi.org/10.1111/j.1476-5381.1995.tb15106.x
  31. Tejedor-Real P, Sahagun M, Biguet NF, Mallet J. Neonatal handling prevents the effects of phencyclidine in an animal model of negative symptoms of schizophrenia. Biol Psychiatry 2007;61:865-872. https://doi.org/10.1016/j.biopsych.2006.08.033
  32. Turgeon SM, Lin T, Subramanian M. Subchronic phencyclidine exposure potentiates the behavioral and c-Fos response to stressful stimuli in rats. Pharmacol Biochem Behav 2007;88:73-81. https://doi.org/10.1016/j.pbb.2007.07.005
  33. Neill JC, Harte MK, Haddad PM, Lydall ES, Dwyer DM. Acute and chronic effects of NMDA receptor antagonists in rodents, relevance to negative symptoms of schizophrenia: a translational link to humans. Eur Neuropsychopharmacol 2014;24:822-835. https://doi.org/10.1016/j.euroneuro.2013.09.011
  34. Chatterjee M, Ganguly S, Srivastava M, Palit G. Effect of 'chronic' versus 'acute' ketamine administration and its 'withdrawal' effect on behavioural alterations in mice: implications for experimental psychosis. Behav Brain Res 2011;216:247-254. https://doi.org/10.1016/j.bbr.2010.08.001
  35. Hou Y, Zhang H, Xie G, Cao X, Zhao Y, Liu Y, et al. Neuronal injury, but not microglia activation, is associated with ketamine-induced experimental schizophrenic model in mice. Prog Neuropsychopharmacol Biol Psychiatry 2013;45:107-116. https://doi.org/10.1016/j.pnpbp.2013.04.006
  36. Ma XC, Dang YH, Jia M, Ma R, Wang F, Wu J, et al. Long-lasting antidepressant action of ketamine, but not glycogen synthase kinase-3 inhibitor SB216763, in the chronic mild stress model of mice. PLoS One 2013;8:e56053. https://doi.org/10.1371/journal.pone.0056053
  37. Tizabi Y, Bhatti BH, Manaye KF, Das JR, Akinfiresoye L. Antidepressant-like effects of low ketamine dose is associated with increased hippocampal AMPA/NMDA receptor density ratio in female Wistar-Kyoto rats. Neuroscience 2012;213:72-80. https://doi.org/10.1016/j.neuroscience.2012.03.052
  38. Neves G, Borsoi M, Antonio CB, Pranke MA, Betti AH, Rates SMK. Is forced swimming immobility a good endpoint for modeling negative symptoms of schizophrenia? - Study of sub-anesthetic ketamine repeated administration effects. An Acad Bras Cienc 2017;89:1655-1669. https://doi.org/10.1590/0001-3765201720160844