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Ketamine induces immediate and delayed alterations of OCD-like behavior

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Abstract

Rationale

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by intrusive obsessive thoughts and/or compulsive behaviors. Currently, serotonin reuptake inhibitors (SRIs) provide the only pharmacological monotherapy for OCD, but response rates are insufficient. Ketamine, a noncompetitive NMDA receptor antagonist, was reported to have rapid, sustained therapeutic effects in OCD patients. However, the mechanisms remain unknown.

Objectives

Here, we aimed to provide a platform for investigating mechanisms underlying anti-OCD effects of ketamine treatment by assessing whether ketamine pretreatment could alleviate 5-HT1B receptor (5-HT1BR)-induced OCD-like behavior in mice.

Methods

We assessed whether acute ketamine (0, 3, 10, 30 mg/kg), administered at two pretreatment time points (30 min, 24 h), would modulate 5-HT1BR-induced OCD-like behavior in mice. Behavioral measures were perseverative hyperlocomotion in the open field and deficits in prepulse inhibition (PPI) induced by acute pharmacological 5-HT1BR challenge.

Results

Three milligrams per kilogram of ketamine reduced 5-HT1BR-induced perseverative hyperlocomotion, but not PPI deficits, 24 h postinjection. In contrast, higher doses of ketamine were either ineffective (10 mg/kg) or exacerbated (30 mg/kg) 5-HT1BR-induced perseverative hyperlocomotion 30 min postinjection. At 24 h postinjection, 30 mg/kg ketamine reduced perseverative hyperlocomotion across all groups.

Conclusions

Our results suggest that the 5-HT1BR-induced model of OCD-like behavior is sensitive to a low dose of ketamine, a potential fast-acting anti-OCD treatment, and may provide a tool for studying mechanisms underlying the rapid therapeutic effects of ketamine in OCD patients.

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References

  • Ahmari SE, Risbrough VB, Geyer MA, Simpson HB (2012) Impaired sensorimotor gating in unmedicated adults with obsessive-compulsive disorder. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 37:1216–1223.

    PubMed  PubMed Central  Google Scholar 

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub

  • Autry AE, Adachi M, Nosyreva E et al (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475:91–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Babyak MA (2004) What you see may not be what you get: a brief, nontechnical introduction to overfitting in regression-type models. Psychosom Med 66:411– 421.

    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

    CAS  PubMed  Google Scholar 

  • Bloch MH, Wasylink S, Landeros-Weisenberger A et al (2012) Effects of ketamine in treatment-refractory obsessive-compulsive disorder. Biol Psychiatry 72:964–970.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chan M-H, Chiu P-H, Lin C-Y, Chen H-H (2012) Inhibition of glycogen synthase kinase-3 attenuates psychotomimetic effects of ketamine. Schizophr Res 136:96–103.

    PubMed  Google Scholar 

  • Chan M-H, Chiu P-H, Sou J-H, Chen H-H (2008) Attenuation of ketamine-evoked behavioral responses by mGluR5 positive modulators in mice. Psychopharmacology 198:141–148.

    CAS  PubMed  Google Scholar 

  • Chaturvedi HK, Dinesh C, Bapna JS (1999) Effect of NMDA receptor antagonists in forced swimming test and its modification by antidepressants. Indian J Pharm 31:104

    CAS  Google Scholar 

  • Choi I-S, Cho J-H, An C-H et al (2012) 5-HT(1B) receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons. Br J Pharmacol 167:356–367.

  • Chowdhury GMI, Behar KL, Cho W, Thomas MA, Rothman DL, Sanacora G (2012) 1H-[13C]-Nuclear magnetic resonance spectroscopy measures of ketamine’s effect on amino acid neurotransmitter metabolism. Biol Psychiatry 71:1022–1025.

    CAS  PubMed  Google Scholar 

  • de Brouwer G, Fick A, Harvey BH, Wolmarans DW (2018) A critical inquiry into marble-burying as a preclinical screening paradigm of relevance for anxiety and obsessive-compulsive disorder: mapping the way forward. Cogn Affect Behav Neurosci 19:1–39.

    Google Scholar 

  • de Oliveira L, Spiazzi CM, Bortolin T et al (2009) Different sub-anesthetic doses of ketamine increase oxidative stress in the brain of rats. Prog Neuro- Psychopharmacol Biol Psychiatry 33:1003–1008.

  • Dold M, Aigner M, Lanzenberger R, Kasper S (2015) Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: an update meta-analysis of double-blind, randomized, placebo-controlled trials. Int J Neuropsychopharmacol Off Sci J Coll Int Neuropsychopharmacol CINP.

  • Douma TN, Millan MJ, Boulay D, Griebel G, Verdouw PM, Westphal KG, Olivier B, Groenink L (2014) CRF1 receptor antagonists do not reverse pharmacological disruption of prepulse inhibition in rodents. Psychopharmacology 231:1289–1303.

    PubMed  Google Scholar 

  • du Jardin KG, Liebenberg N, Cajina M, Müller HK, Elfving B, Sanchez C, Wegener G (2017) S-Ketamine mediates its acute and sustained antidepressant-like activity through a 5-HT1B receptor dependent mechanism in a genetic rat model of depression. Front Pharmacol 8:978.

  • Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, aan het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS (2014) Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry 71:681–688.

    CAS  PubMed  Google Scholar 

  • Fineberg NA, Brown A, Reghunandanan S, Pampaloni I (2012) Evidence-based pharmacotherapy of obsessive-compulsive disorder. Int J Neuropsychopharmacol Off Sci J Coll Int Neuropsychopharmacol CINP 15:1173–1191.

    CAS  PubMed  Google Scholar 

  • Fisher RA (1934) IV: Tests of goodness of fit, independence and homogeneity; WITH TABLE OF X2. In: Statistical Methods for Research Workers, 5th edn. Oliver and Boyd, pp 103–105

  • Fraga DB, Olescowicz G, Moretti M, Siteneski A, Tavares MK, Azevedo D, Colla ARS, Rodrigues ALS (2018) Anxiolytic effects of ascorbic acid and ketamine in mice. J Psychiatr Res 100:16–23.

    PubMed  Google Scholar 

  • Franceschelli A, Sens J, Herchick S et al (2015) Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and “depressed” mice exposed to chronic mild stress. Neuroscience 290:49–60.

    CAS  PubMed  Google Scholar 

  • Gerhard DM, Wohleb ES, Duman RS (2016) Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity. Drug Discov Today 21:454–464.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ghasemi M, Raza M, Dehpour AR (2010) NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test. J Psychopharmacol Oxf Engl 24:585–594.

    PubMed  Google Scholar 

  • Gideons ES, Kavalali ET, Monteggia LM (2014) Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses. Proc Natl Acad Sci U S A 111:8649–8654.

    CAS  Google Scholar 

  • Greist JH, Jefferson JW, Kobak KA, Katzelnick DJ, Serlin RC (1995) Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis. Arch Gen Psychiatry 52:53–60

    CAS  PubMed  Google Scholar 

  • Gross-Isseroff R, Cohen R, Sasson Y, Voet H, Zohar J (2004) Serotonergic dissection of obsessive compulsive symptoms: a challenge study with mchlorophenylpiperazine and sumatriptan. Neuropsychobiology 50:200–205.

    CAS  PubMed  Google Scholar 

  • Guo J-D, O’Flaherty BM, Rainnie DG (2017) Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala. Neuropharmacology 126:224–232.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hayase T, Yamamoto Y, Yamamoto K (2006) Behavioral effects of ketamine and toxic interactions with psychostimulants. BMC Neurosci 7:25.

    PubMed  PubMed Central  Google Scholar 

  • Ho EV, Thompson SL, Katzka WR, Sharifi MF, Knowles JA, Dulawa SC (2016) Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive 10.1007/s00213-019-05397-8 Ho EV, Thompson SL, Katzka WR, Sharifi MF, Knowles JA, Dulawa SC (2016) Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive behavior and striatal activation. Psychopharmacology 233:57–70.

  • Holubova K, Kleteckova L, Skurlova M, Ricny J, Stuchlik A, Vales K (2016) Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner. Psychopharmacology 233:2077–2097.

    CAS  PubMed  Google Scholar 

  • Hou Y, Zhang H, Xie G, Cao X, Zhao Y, Liu Y, Mao Z, Yang J, Wu C (2013) Neuronal injury, but not microglia activation, is associated with ketamine-induced experimental schizophrenic model in mice. Prog Neuro-Psychopharmacol Biol Psychiatry 45:107–116.

    CAS  PubMed  Google Scholar 

  • Imre G, Fokkema DS, Boer JAD, Ter Horst GJ (2006) Dose–response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity. Brain Res Bull 69:338–345.

    CAS  PubMed  Google Scholar 

  • Issaria Y, Jakubovski E, Bartley CA et al (2016) Early onset of response with selective serotonin reuptake inhibitors in obsessive-compulsive disorder: a metaanalysis. J Clin Psychiatry 77:e605–e611.

    PubMed  Google Scholar 

  • Kieschnick R, McCullough BD (2003) Regression analysis of variates observed on (0, 1): percentages, proportions and fractions. Stat Model Int J 3:193–213. https://doi.org/10.1191/1471082X03st053oa

    Article  Google Scholar 

  • Koran LM, Pallanti S, Quercioli L (2001) Sumatriptan, 5-HT(1D) receptors and obsessive-compulsive disorder. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol 11:169–172

    CAS  Google Scholar 

  • Li N, Liu R-J, 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Martinez-Lozano Sinues P, Dallmann R et al (2015) Drug pharmacokinetics determined by real-time analysis of mouse breath. Angew Chem Int Ed 54:7815–7818.

    CAS  PubMed  Google Scholar 

  • Lorrain DS, Baccei CS, Bristow LJ, Anderson JJ, Varney MA (2003) Effects of ketamine and N-methyl-D-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 117:697–706

    CAS  PubMed  Google Scholar 

  • Lu CW, Lin TY, Huang SK, Wang SJ (2018) 5-HT1B receptor agonist CGS12066 presynaptically inhibits glutamate release in rat hippocampus. Prog Neuro- Psychopharmacol Biol Psychiatry 86:122–130.

    CAS  PubMed  Google Scholar 

  • Maeng S, Zarate CA, Du J et al (2008) Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole- 4-propionic acid receptors. Biol Psychiatry 63:349–352.

  • McGowan JC, LaGamma CT, Lim SC, Tsitsiklis M, Neria Y, Brachman RA, Denny CA (2017) Prophylactic ketamine attenuates learned fear. Neuropsychopharmacology 42:1577–1589.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moghaddam B, Adams B, Verma A, Daly D (1997) 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 17:2921–2927

    CAS  PubMed  PubMed Central  Google Scholar 

  • Montgomery SA, Manceaux A (1992) Fluvoxamine in the treatment of obsessive compulsive disorder. Int Clin Psychopharmacol:5–10

    PubMed  Google Scholar 

  • Oberlander C, Demassey Y, Verdu A, van de Velde D, Bardelay C (1987) Tolerance to the serotonin 5-HT1 agonist RU 24969 and effects on dopaminergic behaviour. Eur J Pharmacol 139:205–214

    CAS  PubMed  Google Scholar 

  • Ossato A, Bilel S, Gregori A, Talarico A, Trapella C, Gaudio RM, de-Giorgio F, Tagliaro F, Neri M, Fattore L, Marti M (2018) Neurological, sensorimotor and cardiorespiratory alterations induced by methoxetamine, ketamine and phencyclidine in mice. Neuropharmacology 141:167–180.

    CAS  PubMed  Google Scholar 

  • Paulus MP, Geyer MA (1991a) A temporal and spatial scaling hypothesis for the behavioral effects of psychostimulants. Psychopharmacology 104:6–16

    CAS  PubMed  Google Scholar 

  • Paulus MP, Geyer MA (1991b) A scaling approach to find order parameters quantifying the effects of dopaminergic agents on unconditioned motor activity in rats. Prog Neuro-Psychopharmacol Biol Psychiatry 15:903–919.

    CAS  PubMed  Google Scholar 

  • Popik P, Hołuj M, Kos T, Nowak G, Librowski T, Sałat K (2017) Comparison of the psychopharmacological effects of tiletamine and ketamine in rodents. Neurotox Res 32:544–554.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Popik P, Kos T, Sowa-Kućma M, Nowak G (2008) Lack of persistent effects of ketamine in rodent models of depression. Psychopharmacology 198:421–430.

    CAS  PubMed  Google Scholar 

  • Radford KD, Park TY, Lee BH et al (2017) Dose-response characteristics of intravenous ketamine on dissociative stereotypy, locomotion, sensorimotor gating, and nociception in male Sprague-Dawley rats. Pharmacol Biochem Behav 153:130–140.

    CAS  Google Scholar 

  • Razoux F, Garcia R, Léna I (2007) Ketamine, at a dose that disrupts motor behavior and latent inhibition, enhances prefrontal cortex synaptic efficacy and glutamate release in the nucleus accumbens. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 32:719–727.

    PubMed  Google Scholar 

  • Refsgaard LK, Pickering DS, Andreasen JT (2017) Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four Nmethyl-D-aspartate receptor antagonists in mice. Behav Pharmacol 28:37–47.

    CAS  PubMed  Google Scholar 

  • Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, Flood P, Simpson HB (2013) Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 38:2475–2483. 10.1007/s00213-019-05397-8 obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 38:2475–2483.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rodriguez CI, Wheaton M, Zwerling J et al (2016) Can exposure-based CBT extend the effects of intravenous ketamine in obsessive-compulsive disorder? an open-label trial. J Clin Psychiatry 77:408–409.

    PubMed  PubMed Central  Google Scholar 

  • Ruscio AM, Stein DJ, Chiu WT, Kessler RC (2010) The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry 15:53–63.

    PubMed  PubMed Central  Google Scholar 

  • Sałat K, Siwek A, Starowicz G et al (2015) Antidepressant-like effects of ketamine, norketamine and dehydronorketamine in forced swim test: Role of activity at NMDA receptor. Neuropharmacology 99:301–307.

    PubMed  Google Scholar 

  • Shanahan NA, Holick Pierz KA, Masten VL, Waeber C, Ansorge M, Gingrich JA, Geyer MA, Hen R, Dulawa SC (2009) Chronic reductions in serotonin transporter function prevent 5-HT1B-induced behavioral effects in mice. Biol Psychiatry 65:401–408.

    CAS  PubMed  Google Scholar 

  • Shanahan NA, Velez LP, Masten VL, Dulawa SC (2011) Essential role for orbitofrontal serotonin 1B receptors in obsessive-compulsive disorder-like behavior and serotonin reuptake inhibitor response in mice. Biol Psychiatry 70:1039–1048.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Smithson M, Verkuilen J (2006) A better lemon squeezer? Maximum-likelihood regression with beta-distributed dependent variables. Psychol Methods 11:54–71.

    PubMed  Google Scholar 

  • Soumier A, Carter RM, Schoenfeld TJ, Cameron HA (2016) New hippocampal neurons mature rapidly in response to ketamine but are not required for its acute antidepressant effects on neophagia in rats. eNeuro 3:.

    PubMed  PubMed Central  Google Scholar 

  • Stein DJ, Van Heerden B, Wessels CJ et al (1999) Single photon emission computed tomography of the brain with Tc-99 m HMPAO during sumatriptan challenge in obsessive-compulsive disorder: investigating the functional role of the serotonin auto-receptor. Prog Neuro-Psychopharmacol Biol Psychiatry 23:1079–1099

    CAS  Google Scholar 

  • Stern ER, Taylor SF (2014) Cognitive neuroscience of obsessive-compulsive disorder. Psychiatr Clin North Am 37:337–352.

    Google Scholar 

  • Thelen C, Flaherty E, Saurine J, Sens J, Mohamed S, Pitychoutis PM (2019) Sex differences in the temporal neuromolecular and synaptogenic effects of the rapidacting antidepressant drug ketamine in the mouse brain. Neuroscience 398:182–192.

    CAS  PubMed  Google Scholar 

  • Thompson SL, Dulawa SC (2019) Dissecting the roles of β-arrestin2 and GSK-3 signaling in 5-HT1BR-mediated perseverative behavior and prepulse inhibition deficits in mice. PLoS One 14:e0211239.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson SL, Dulawa SC (2017) Pharmacological and behavioral rodent models of OCD. In: Pittenger C (ed) Obsessive-Compulsive Disorder: Phenomenology, Pathophysiology, and Treatment. Oxford University Press, pp 385–400

  • Tosta CL, Silote GP, Fracalossi MP, Sartim AG, Andreatini R, Joca SRL, Beijamini V (2019) S-ketamine reduces marble burying behaviour: involvement of ventromedial orbitofrontal cortex and AMPA receptors. Neuropharmacology 144:233–243.

    CAS  PubMed  Google Scholar 

  • Veale D, Miles S, Smallcombe N, Ghezai H, Goldacre B, Hodsoll J (2014) Atypical antipsychotic augmentation in SSRI treatment refractory obsessivecompulsive disorder: a systematic review and meta-analysis. BMC Psychiatry 14:317.

  • Wu SY, Wang MY, Dun NJ (1991) Serotonin via presynaptic 5-HT1 receptors attenuates synaptic transmission to immature rat motoneurons in vitro. Brain Res 554:111–121.

    CAS  PubMed  Google Scholar 

  • Yamanaka H, Yokoyama C, Mizuma H, Kurai S, Finnema SJ, Halldin C, Doi H, Onoe H (2014) A possible mechanism of the nucleus accumbens and ventral pallidum 5-HT1B receptors underlying the antidepressant action of ketamine: a PET study with macaques. Transl Psychiatry 4:e342.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 533:481–486.

  • Zanos P, Nelson ME, Highland JN, et al (2017) A negative allosteric modulator for α5 subunit-containing GABA receptors exerts a rapid and persistent antidepressant-like action without the side effects of the NMDA receptor antagonist ketamine in mice. eNeuro 4:.

    PubMed  PubMed Central  Google Scholar 

  • Zanos P, Piantadosi SC, Wu H-Q et al (2015) The prodrug 4-chlorokynurenine causes ketamine-like antidepressant effects, but not side effects, by NMDA/GlycineB-Site Inhibition. J Pharmacol Exp Ther 355:76–85.

    CAS  Google Scholar 

  • Zarate CA, Singh JB, Carlson PJ et al (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856–864.

    CAS  PubMed  Google Scholar 

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Funding and disclosures

This work was supported by an IMHRO Rising Star Depression Research Award in Memory of George Largay, a NARSAD Independent Investigator Award , and R21MH115395 to SD, and training grants: T32 GM07839 and T32 DA07255 to SLT.

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Authors and Affiliations

  1. Committee on Neurobiology, University of Chicago, Chicago, IL, 60637, USA

    Summer L. Thompson

  2. Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA

    Summer L. Thompson, Amanda C. Welch & Stephanie C. Dulawa

  3. University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA

    Julia Iourinets

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  1. Summer L. Thompson
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Correspondence to Stephanie C. Dulawa.

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Thompson, S.L., Welch, A.C., Iourinets, J. et al. Ketamine induces immediate and delayed alterations of OCD-like behavior. Psychopharmacology 237, 627–638 (2020). https://doi.org/10.1007/s00213-019-05397-8

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