GLYX-13 Produces Rapid Antidepressant Responses with Key Synaptic and Behavioral Effects Distinct from Ketamine
Open accessAbstract
GLYX-13 is a putative NMDA receptor modulator with glycine-site partial agonist properties that produces rapid antidepressant effects, but without the psychotomimetic side effects of ketamine. Studies were conducted to examine the molecular, cellular, and behavioral actions of GLYX-13 to further characterize the mechanisms underlying the antidepressant actions of this agent. The results demonstrate that a single dose of GLYX-13 rapidly activates the mTORC1 pathway in the prefrontal cortex (PFC), and that infusion of the selective mTORC1 inhibitor rapamycin into the medial PFC (mPFC) blocks the antidepressant behavioral actions of GLYX-13, indicating a requirement for mTORC1 similar to ketamine. The results also demonstrate that GLYX-13 rapidly increases the number and function of spine synapses in the apical dendritic tuft of layer V pyramidal neurons in the mPFC. Notably, GLYX-13 significantly increased the synaptic responses to hypocretin, a measure of thalamocortical synapses, compared with its effects on 5-HT responses, a measure of cortical-cortical responses mediated by the 5-HT 2A receptor. Behavioral studies further demonstrate that GLYX-13 does not influence 5-HT 2 receptor induced head twitch response or impulsivity in a serial reaction time task (SRTT), whereas ketamine increased responses in both tests. In contrast, both GLYX-13 and ketamine increased attention in the SRTT task, which is linked to hypocretin-thalamocortical responses. The differences in the 5-HT 2 receptor synaptic and behavioral responses may be related to the lack of psychotomimetic side effects of GLYX-13 compared with ketamine, whereas regulation of the hypocretin responses may contribute to the therapeutic benefits of both rapid acting antidepressants.
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Rapastinel reverses synaptic plasticity deficits and exhibits antidepressant-like effects in rodent models.
“Of note, however, rapastinel, another drug that reverses synaptic plasticity deficits and exhibits antidepressant-like effects in rodent models 36,37 , has been studied in 3 clinical trials to date with relatively weak evidence for its efficacy 38 .”
From Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model (2020) · cites this paper as [36]
The GLYX-13 Increases mTORC1 Signaling in the PFC section reports antidepressant-like effects of GLYX-13 (rapastinel) in rodent behavioral tests, and the synaptic-results section reports increased dendritic spine density. The Discussion does not show that GLYX-13 reverses an existing synaptic plasticity deficit; it attributes reversal of stress-related synaptic deficits to ketamine. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSeveral ketamine-like glutamate modulators, including AXS-05 and esketamine, are under investigation by pharmaceutical companies and in Clinical Trial phases II and III for depression.
“Several ketamine-like glutamate modulators, including AXS-05 and esketamine, are under investigation by pharmaceutical companies and in Clinical Trial phases II and III for depression (Liu et al, 2016;Murrough, 2016).”
From Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial (2018) · cites this paper as Liu et al, 2016
The Introduction (page unavailable) describes GLYX-13 as a glutamatergic compound with preliminary evidence of antidepressant effects in patients, and the Funding section identifies support from Naurex. This supports the general point that a ketamine-related glutamate modulator was being investigated for depression. The paper does not identify AXS-05 or esketamine or establish phase II or III trial status for them. (LLM, conf=0.82)
Experimental — accuracy not yet measuredA single dose of ketamine (10 mg/kg) produced similar effects on mTORC1 signaling proteins.
“A single dose of ketamine (10 mg/kg) produced effects (Figure 4, C-E) similar to those previously reported (7, 8, 11, 24).”
From Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation (2019) · cites this paper as [11]
Many forms of activity-dependent plasticity are likely NMDAR-dependent, supported by the antidepressant-like actions of GLYX-13 in preclinical models.
“Many of these forms of activity-dependent plasticity are likely to be NMDAR-dependent, as supported by the antidepressant-like actions of the NMDAR positive allosteric modulator GLYX-13 (rapastinel) in preclinical models [213].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [213]
Partial agonists at the NMDAR glycineB binding site, including GLYX-13 and D-cycloserine, manifest antidepressant effects in clinical trials and animal tests without sharing ketamine's NMDAR inhibition-mediated side effects.
“Another finding challenging the NMDAR inhibition hypothesis of ketamine’s antidepressant mechanism of action is the fact that partial agonists at the NMDAR glycineB binding site, including GLYX-13 (i.e., rapastinel) and D-cycloserine manifest antidepressant effects in clinical trials 104, 105 and in animal tests 106–109, without sharing ketamine’s NMDAR inhibition-mediated side effects 109.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [108]
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Cites
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,501 · see citing works
Trivedi, M. H., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Warden, D., Ritz, L., Norquist, G., Howland, R. H., Lebowitz, B., McGrath, P. J., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.1.28 · Cited by 3,879 · see citing works
Antidepressant effects of ketamine in depressed patients
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00230-9 · Cited by 3,856 · see citing works
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568 · see citing works
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
Li, N., Lee, B., Liu, R.-J., Banasr, M., Dwyer, J. M., Iwata, M., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2010) · Science · doi:10.1126/science.1190287 · Cited by 2,881 · see citing works
Self-citationNMDA receptor blockade at rest triggers rapid behavioural antidepressant responses
Autry, A. E., Adachi, M., Nosyreva, E., Na, E. S., Los, M. F., Cheng, P.-F., Kavalali, E. T., & Monteggia, L. M. (2011) · Nature · doi:10.1038/nature10130 · Cited by 1,926 · see citing works
Moghaddam, B., Adams, B., Verma, A., & Daly, D. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-08-02921.1997 · Cited by 1,793 · see citing works
Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016) · Nature Medicine · doi:10.1038/nm.4050 · Cited by 1,750 · see citing works
Self-citationSynaptic Dysfunction in Depression: Potential Therapeutic Targets
Duman, R. S., & Aghajanian, G. K. (2012) · Science · doi:10.1126/science.1222939 · Cited by 1,651 · see citing works
Self-citationHomayoun, H., & Moghaddam, B. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2213-07.2007 · Cited by 1,231 · see citing works
mTOR signaling: At the crossroads of plasticity, memory and disease
Hoeffer, C. A., & Klann, E. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2009.11.003 · Cited by 1,128 · see citing works
Maeng, S., Zarate, C. A., Du, J., Schloesser, R. J., McCammon, J., Chen, G., & Manji, H. K. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.028 · Cited by 1,103 · see citing works
Li, N., Liu, R.-J., Dwyer, J. M., Banasr, M., Lee, B., Son, H., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.12.015 · Cited by 1,082 · see citing works
Self-citationRodriguez, A., Ehlenberger, D. B., Dickstein, D. L., Hof, P. R., & Wearne, S. L. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001997 · Cited by 571 · see citing works
Bari, A., Dalley, J. W., & Robbins, T. W. (2008) · Nature Protocols · doi:10.1038/nprot.2008.41 · Cited by 452 · see citing works
VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants
Warner-Schmidt, J. L., & Duman, R. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610282104 · Cited by 438 · see citing works
Self-citationAbdallah, C. G., Sanacora, G., Duman, R. S., & Krystal, J. H. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-053013-062946 · Cited by 422 · see citing works
Self-citationLiu, R.-J., Lee, F. S., Li, X.-Y., Bambico, F., Duman, R. S., & Aghajanian, G. K. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.09.030 · Cited by 403 · see citing works
Self-citationZhou, W., Wang, N., Yang, C., Li, X.-M., Zhou, Z.-Q., & Yang, J.-J. (2014) · European Psychiatry · doi:10.1016/j.eurpsy.2013.10.005 · Cited by 390 · see citing works
The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder
Jernigan, C. S., Goswami, D. B., Austin, M. C., Iyo, A. H., Chandran, A., Stockmeier, C. A., & Karolewicz, B. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.05.010 · Cited by 386 · see citing works
Miller, O. H., Yang, L., Wang, C.-C., Hargroder, E. A., Zhang, Y., Delpire, E., & Hall, B. J. (2014) · eLife · doi:10.7554/elife.03581 · Cited by 358 · see citing works
Liu, R.-J., & Aghajanian, G. K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706679105 · Cited by 346 · see citing works
Self-citationBurgdorf, J., Zhang, X.-L., Nicholson, K. L., Balster, R. L., David Leander, J., Stanton, P. K., Gross, A. L., Kroes, R. A., & Moskal, J. R. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.246 · Cited by 284 · see citing works
Self-citationREDD1 is essential for stress-induced synaptic loss and depressive behavior
Ota, K. T., Liu, R.-J., Voleti, B., Maldonado-Aviles, J. G., Duric, V., Iwata, M., Dutheil, S., Duman, C., Boikess, S., Lewis, D. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3513 · Cited by 267 · see citing works
Self-citationFuchikami, M., Thomas, A., Liu, R., Wohleb, E. S., Land, B. B., DiLeone, R. J., Aghajanian, G. K., & Duman, R. S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414728112 · Cited by 265 · see citing works
Self-citationLiu, R.-J., Fuchikami, M., Dwyer, J. M., Lepack, A. E., Duman, R. S., & Aghajanian, G. K. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.128 · Cited by 256 · see citing works
Self-citationSex differences in the antidepressant-like effects of ketamine
Carrier, N., & Kabbaj, M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.12.009 · Cited by 251 · see citing works
Willins, D. L., & Meltzer, H. Y. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36840-5 · Cited by 244 · see citing works
Winstanley, C. A., Chudasama, Y., Dalley, J. W., Theobald, D. E. H., Glennon, J. C., & Robbins, T. W. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1398-x · Cited by 234 · see citing works
Characterization of the head-twitch response induced by hallucinogens in mice
Halberstadt, A. L., & Geyer, M. A. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3006-z · Cited by 216 · see citing works
The Female Urine Sniffing Test: A Novel Approach for Assessing Reward-Seeking Behavior in Rodents
Malkesman, O., Scattoni, M. L., Paredes, D., Tragon, T. R., Pearson, B. L., Shaltiel, G., Chen, G., Crawley, J. N., & Manji, H. K. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.10.018 · Cited by 197 · see citing works
De Gois, S., Schäfer, M. K.-H., Defamie, N., Chen, C., Ricci, A., Weihe, E., Varoqui, H., & Erickson, J. D. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5221-04.2005 · Cited by 192 · see citing works
Yang, C., Hu, Y.-M., Zhou, Z.-Q., Zhang, G.-F., & Yang, J.-J. (2013) · Upsala Journal of Medical Sciences · doi:10.3109/03009734.2012.724118 · Cited by 173 · see citing works
mTOR activation is required for the antidepressant effects of mGluR2/3 blockade
Dwyer, J. M., Lepack, A. E., & Duman, R. S. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711001702 · Cited by 169 · see citing works
Self-citationAkinfiresoye, L. R., & Tizabi, Y. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3153-2 · Cited by 149 · see citing works
Lambe, E. K., Olausson, P., Horst, N. K., Taylor, J. R., & Aghajanian, G. K. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.0719-05.2005 · Cited by 135 · see citing works
Self-citationLambe, E. K., & Aghajanian, G. K. (2003) · Neuron · doi:10.1016/s0896-6273(03)00598-1 · Cited by 127 · see citing works
Self-citationPaul, R. K., Singh, N. S., Khadeer, M., Moaddel, R., Sanghvi, M., Green, C. E., O’Loughlin, K., Torjman, M. C., Bernier, M., & Wainer, I. W. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000285 · Cited by 115 · see citing works
Zhang, X.-L., Sullivan, J. A., Moskal, J. R., & Stanton, P. K. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.08.018 · Cited by 107 · see citing works
Self-citationAntidepressant action of ketamine via mTOR is mediated by inhibition of nitrergic Rheb degradation
Harraz, M. M., Tyagi, R., Cortés, P., & Snyder, S. H. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.211 · Cited by 94 · see citing works
Moskal, J. R., Kuo, A. G., Weiss, C., Wood, P. L., Hanson, A. O., Kelso, S. R., Harris, R. B., & Disterhoft, J. F. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.06.006 · Cited by 92 · see citing works
Self-citationThe Development of Rapastinel (Formerly GLYX-13); A Rapid Acting and Long Lasting Antidepressant
Moskal, J. R., Burgdorf, J. S., Stanton, P. K., Kroes, R. A., Disterhoft, J. F., Burch, R. M., & Khan, M. A. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666160321122703 · Cited by 92 · see citing works
Self-citationRole of Orexin in the Pathophysiology of Depression: Potential for Pharmacological Intervention
Nollet, M., & Leman, S. (2013) · CNS Drugs · doi:10.1007/s40263-013-0064-z · Cited by 89 · see citing works
Burgdorf, J., Zhang, X.-L., Weiss, C., Gross, A., Boikess, S. R., Kroes, R. A., Khan, M. A., Burch, R. M., Rex, C. S., Disterhoft, J. F., et al. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.09.004 · Cited by 88 · see citing works
Self-citationLu, Y., Wang, C., Xue, Z., Li, C., Zhang, J., Zhao, X., Liu, A., Wang, Q., & Zhou, W. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu110 · Cited by 74 · see citing works
Chiu, C., Scheuing, L., Liu, G., Liao, H., Linares, G. R., Lin, D. H., & Chuang, D. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu102 · Cited by 66 · see citing works
Klein, A. B., Ultved, L., Adamsen, D., Santini, M. A., Tobeña, A., Fernández‐Teruel, A., Flores, P., Moreno, M., Cardona, D., Knudsen, G. M., et al. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2013.12.063 · Cited by 63 · see citing works
Liu, R.-J., Ota, K. T., Dutheil, S., Duman, R. S., & Aghajanian, G. K. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.70 · Cited by 59 · see citing works
Self-citationBurgdorf, J. S., Kroes, R. A., Zhang, X.-L., Gross, A. L., Schmidt, M. E., Weiss, C., Disterhoft, J. F., Burch, R. M., Stanton, P. K., & Moskal, J. R. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.07.039 · Cited by 58 · see citing works
Self-citationRajagopal, L., Burgdorf, J. S., Moskal, J. R., & Meltzer, H. Y. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.10.060 · Cited by 45 · see citing works
Self-citationMultiple Non-Equivalent Interfaces Mediate Direct Activation of GABAA Receptors by Propofol
Eaton, M. M., Germann, A. L., Arora, R., Cao, L. Q., Gao, X., Shin, D. J., Wu, A., Chiara, D. C., Cohen, J. B., Steinbach, J. H., et al. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666160202121319 · Cited by 44 · see citing works
Aghajanian, G. K. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1484-9 · Cited by 38 · see citing works
Self-citationPopp, S., Behl, B., Joshi, J. J., Lanz, T. A., Spedding, M., Schenker, E., Jay, T. M., Svenningsson, P., Caudal, D., Cunningham, J. I., et al. (2016) · F1000Research · doi:10.12688/f1000research.8236.1 · Cited by 35 · see citing works
Yang, C., Li, W.-Y., Yu, H.-Y., Gao, Z.-Q., Liu, X.-L., Zhou, Z.-Q., & Yang, J.-J. (2012) · Journal of Biomedicine and Biotechnology · doi:10.1155/2012/175619 · Cited by 29 · see citing works
Acute ketamine-induced neuroplasticity
Tedesco, V., Ravagnani, C., Bertoglio, D., & Chiamulera, C. (2013) · Neuroreport · doi:10.1097/wnr.0b013e32836131ad · Cited by 23 · see citing works
Chronic nicotine attenuates phencyclidine-induced impulsivity in a mouse serial reaction time task
Scott, D., & Taylor, J. R. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.11.009 · Cited by 13 · see citing works
Self-citationYoshizawa, K., Mori, T., Ueno, T., Nishiwaki, M., Shibasaki, M., Shimizu, N., Narita, M., & Suzuki, T. (2013) · Journal of Pharmacological Sciences · doi:10.1254/jphs.12148sc · Cited by 11 · see citing works
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1 of the 58 references couldn’t be matched to a known paper.
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Mechanisms of ketamine action as an antidepressant
Zanos, P., & Gould, T. D. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.255 · Cited by 1,127 · see citing works
Duman, R. S., Sanacora, G., & Krystal, J. H. (2019) · Neuron · doi:10.1016/j.neuron.2019.03.013 · Cited by 1,026 · see citing works
Self-citationNeuroplasticity in cognitive and psychological mechanisms of depression: an integrative model
Price, R. B., & Duman, R. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0615-x · Cited by 721 · see citing works
Self-citationDendritic structural plasticity and neuropsychiatric disease
Forrest, M. P., Parnell, E., & Penzes, P. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.16 · Cited by 464 · see citing works
Targeting glutamate signalling in depression: progress and prospects
Murrough, J. W., Abdallah, C. G., & Mathew, S. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.16 · Cited by 482 · see citing works
Hashimoto, K. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12902 · Cited by 335 · see citing works
Wohleb, E. S., Terwilliger, R., Duman, C. H., & Duman, R. S. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.05.026 · Cited by 288 · see citing works
Self-citationPsychoplastogens: A promising class of plasticity-promoting neurotherapeutics
Olson, D. E. (2018) · Journal of Experimental Neuroscience · doi:10.1177/1179069518800508 · Cited by 257 · see citing works
Abdallah, C. G., Sanacora, G., Duman, R. S., & Krystal, J. H. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.05.010 · Cited by 219 · see citing works
Self-citationKetamine and rapid-acting antidepressants: a new era in the battle against depression and suicide
Duman, R. S. (2018) · F1000Research · doi:10.12688/f1000research.14344.1 · Cited by 208 · see citing works
Self-citationSales, A. J., Fogaça, M. V., Sartim, A. G., Pereira, V. S., Wegener, G., Guimarães, F. S., & Joca, S. R. L. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1143-4 · Cited by 199 · see citing works
Fukumoto, K., Fogaça, M. V., Liu, R.-J., Duman, C., Kato, T., Li, X.-Y., & Duman, R. S. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814709116 · Cited by 188 · see citing works
Self-citationNeurotrophic mechanisms underlying the rapid and sustained antidepressant actions of ketamine
Deyama, S., & Duman, R. S. (2020) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.172837 · Cited by 186 · see citing works
Self-citationConvergent Mechanisms Underlying Rapid Antidepressant Action
Zanos, P., Thompson, S. M., Duman, R. S., Zarate, C. A., & Gould, T. D. (2018) · CNS Drugs · doi:10.1007/s40263-018-0492-x · Cited by 171 · see citing works
Self-citationGlutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments
Kadriu, B., Musazzi, L., Henter, I. D., Graves, M., Popoli, M., & Zarate, C. A. (2019) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyy094 · Cited by 165 · see citing works
Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function
Duman, R. S., Shinohara, R., Fogaça, M. V., & Hare, B. D. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0400-x · Cited by 155 · see citing works
Self-citationKetamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial
Taylor, J. H., Landeros-Weisenberger, A., Coughlin, C., Mulqueen, J., Johnson, J. A., Gabriel, D., Reed, M. O., Jakubovski, E., & Bloch, M. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.194 · Cited by 142 · see citing works
Self-citationMolecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants
Gould, T. D., Zarate, C. A., & Thompson, S. M. (2019) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010617-052811 · Cited by 133 · see citing works
“Upregulation of AMPAR synaptic expression has been measured in immunoblots from animals within 24 hours after treatment with ketamine and other putative rapid-acting antidepressant drugs (68, 71, 107, 129, 139).”
BackgroundKetamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression
Lener, M. S., Kadriu, B., & Zarate, C. A. (2017) · Drugs · doi:10.1007/s40265-017-0702-8 · Cited by 131 · see citing works
Deyama, S., Bang, E., Kato, T., Li, X.-Y., & Duman, R. S. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.12.014 · Cited by 116 · see citing works
Self-citationSynaptic Mechanisms Regulating Mood State Transitions in Depression
Parekh, P. K., Johnson, S. B., & Liston, C. (2022) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-110920-040422 · Cited by 101 · see citing works
Dunlap, L. E., Azinfar, A., Ly, C., Cameron, L. P., Viswanathan, J., Tombari, R. J., Myers-Turnbull, D., Taylor, J. C., Grodzki, A. C., Lein, P. J., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01404 · Cited by 95 · see citing works
Self-citationBDNF Release and Signaling Are Required for the Antidepressant Actions of GLYX-13
Kato, T., Fogaça, M. V., Deyama, S., Li, X.-Y., Fukumoto, K., & Duman, R. S. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.220 · Cited by 88 · see citing works
Self-citationSestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation
Kato, T., Pothula, S., Liu, R.-J., Duman, C. H., Terwilliger, R., Vlasuk, G. P., Saiah, E., Hahm, S., & Duman, R. S. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126859 · Cited by 88 · see citing works
Self-citationKetamine and the Future of Rapid-Acting Antidepressants
Riggs, L. M., & Gould, T. D. (2021) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-072120-014126 · Cited by 87 · see citing works
Cell-type specific modulation of NMDA receptors triggers antidepressant actions
Pothula, S., KATO, T., Liu, R.-J., Wu, M., Gerhard, D. M., Shinohara, R., Sliby, A., Chowdhury, G. M. I., Behar, K. L., Sanacora, G., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0796-3 · Cited by 81 · see citing works
Self-citationFogaça, M. V., Fukumoto, K., Franklin, T., Liu, R.-J., Duman, C. H., Vitolo, O. V., & Duman, R. S. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0501-x · Cited by 82 · see citing works
Self-citationResolvin E1/E2 ameliorate lipopolysaccharide-induced depression-like behaviors via ChemR23
Deyama, S., Shimoda, K., Suzuki, H., Ishikawa, Y., Ishimura, K., Fukuda, H., HitoraーImamura, N., Ide, S., Satoh, M., Kaneda, K., et al. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4774-7 · Cited by 78 · see citing works
Witkin, J. M., Martin, A. E., Golani, L. K., Xu, N. Z., & Smith, J. L. (2019) · Advances in pharmacology · doi:10.1016/bs.apha.2019.03.002 · Cited by 75 · see citing works
Rapid Acting Antidepressants in Chronic Stress Models: Molecular and Cellular Mechanisms
Hare, B. D., Ghosal, S., & Duman, R. S. (2017) · Chronic Stress · doi:10.1177/2470547017697317 · Cited by 67 · see citing works
Self-citationLee, M. T., Peng, W., Kan, H., Wu, C., Wang, D., & Ho, Y. (2022) · Biomedicines · doi:10.3390/biomedicines10051005 · Cited by 67 · see citing works
Klass, A., Sánchez-Porras, R., & Santos, E. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18771440 · Cited by 57 · see citing works
Role of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy
Jiang, C. S., Lin, W., & Salton, S. R. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1124-0 · Cited by 55 · see citing works
Fukumoto, K., Fogaça, M. V., Liu, R.-J., Duman, C. H., Li, X., Chaki, S., & Duman, R. S. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0705-0 · Cited by 55 · see citing works
Self-citationRapid-Acting Antidepressants: Mechanistic Insights and Future Directions
Gerhard, D. M., & Duman, R. S. (2018) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-018-0139-8 · Cited by 52 · see citing works
Self-citationDonello, J. E., Banerjee, P., Li, Y.-X., Guo, Y.-X., Yoshitake, T., Zhang, X.-L., Miry, O., Kehr, J., Stanton, P. K., Gross, A. L., et al. (2019) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyy101 · Cited by 50 · see citing works
Self-citationKATO, T., & Duman, R. S. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.172827 · Cited by 49 · see citing works
Self-citationWang, Y., Zhang, N., Liu, L., Jiang, H., Hu, D., Wang, Z., Chen, N., & Zhang, Y. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.01.024 · Cited by 46 · see citing works
Bollinger, J. L., Horchar, M. J., & Wohleb, E. S. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0720-1 · Cited by 44 · see citing works
Witkin, J. M., Knutson, D. E., Rodriguez, G. J., & Shi, S. X.-Y. (2018) · Current Pharmaceutical Design · doi:10.2174/1381612824666180730104707 · Cited by 44 · see citing works
Camargo, A., Pazini, F. L., Rosa, J. M., Wolin, I. A. V., Moretti, M., da Rosa, P. B., Neis, V. B., & Rodrigues, A. L. S. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.05.017 · Cited by 44 · see citing works
Liu, W., Li, Y., Zhao, T., Gong, M., Wang, X., Zhang, Y., Xu, L., Li, W., Li, Y., & Jia, J. (2023) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2023.102534 · Cited by 43 · see citing works
Neural plasticity and depression treatment
Wang, Y., Song, N., Ding, Y., & Zhang, L. (2022) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2022.09.001 · Cited by 44 · see citing works
Engaging homeostatic plasticity to treat depression
Workman, E. R., Niere, F., & Raab‐Graham, K. F. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.225 · Cited by 42 · see citing works
Plasticity of synapses and reward circuit function in the genesis and treatment of depression
Thompson, S. M. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-022-01422-1 · Cited by 40 · see citing works
Beyond Ketamine: New Approaches to the Development of Safer Antidepressants
Chaki, S. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170221101054 · Cited by 40 · see citing works
Hyperforin Potentiates Antidepressant-Like Activity of Lanicemine in Mice
Pochwat, B., Szewczyk, B., Kotarska, K., Rafało-Ulińska, A., Siwiec, M., Sowa, J. E., Tokarski, K., Siwek, A., Bouron, A., Friedland, K., et al. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00456 · Cited by 37 · see citing works
Rapid acting antidepressants in the mTOR pathway: Current evidence
Athira, K. V., Mohan, A. S., & Chakravarty, S. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.07.022 · Cited by 33 · see citing works
Abdallah, C. G., Ahn, K.-H., Averill, L. A., Nemati, S., Averill, C. L., Fouda, S., Ranganathan, M., MORGAN, P. T., D’Souza, D. C., Mathalon, D. H., et al. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-00864-9 · Cited by 33 · see citing works
Pothula, S., Liu, R.-J., Wu, M., Sliby, A., Picciotto, M. R., Banerjee, P., & Duman, R. S. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-00882-7 · Cited by 32 · see citing works
Self-citationIntrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review
Demchenko, I., Tassone, V. K., Kennedy, S. H., Dunlop, K., & Bhat, V. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.864902 · Cited by 29 · see citing works
“This might partially explain why rapastinel, an NMDA-R allosteric modulator with glycine-site partial agonist properties, failed in TRD clinical trials despite its ability to increase PFC synaptic connectivity (214, 215).”
BackgroundPochwat, B., Rafało-Ulińska, A., Domin, H., Misztak, P., Nowak, G., & Szewczyk, B. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.08.006 · Cited by 30 · see citing works
Llamosas, N., Pérez-Caballero, L., Berrocoso, E., Bruzos-Cidón, C., Ugedo, L., & Torrecilla, M. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.07.022 · Cited by 31 · see citing works
Chen, S., Hsieh, C.-P., Lee, M.-Y., Chen, L.-C., Huang, C.-M., Chen, H., & Chan, M. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112369 · Cited by 28 · see citing works
Antidepressant-like effect of guanosine involves activation of AMPA receptor and BDNF/TrkB signaling
da Rosa, P. B., Bettio, L. E. B., Neis, V. B., Moretti, M., Kaufmann, F. N., Tavares, M. K., Werle, I., Dalsenter, Y. D. O., Platt, N., Rosado, A. F., et al. (2021) · Purinergic Signalling · doi:10.1007/s11302-021-09779-6 · Cited by 26 · see citing works
KATO, T. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109325 · Cited by 24 · see citing works
Self-citationPerisynaptic astrocytes as a potential target for novel antidepressant drugs
Frizzo, M. E., & Ohno, Y. (2020) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2020.11.002 · Cited by 24 · see citing works
Wierońska, J. M., & Pilc, A. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.08.010 · Cited by 23 · see citing works
Ketamine and rapid acting antidepressants: Are we ready to cure, rather than treat depression?
Abdallah, C. G., & Krystal, J. H. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112628 · Cited by 23 · see citing works
Chen, F., Li, L., Huang, M., Wang, Y., Wang, L., Jin, F., Yang, L., Gao, M., Li, L., Wang, Y., et al. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155452 · Cited by 22 · see citing works
ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in mice
Shen, M., Lv, D., Liu, X., & Wang, C. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02290-5 · Cited by 22 · see citing works
Vasilescu, A.-N., Schweinfurth, N., Borgwardt, S., Gass, P., Lang, U. E., Inta, D., & Eckart, S. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s119004 · Cited by 21 · see citing works
He, Z., Song, H., Liu, T., Ma, J., Xing, Z., Yin, Y.-Y., Liu, L., Zhang, Y.-N., Zhao, Y., Yu, H., et al. (2019) · Cerebral Cortex · doi:10.1093/cercor/bhz036 · Cited by 20 · see citing works
Yang, P.-S., Peng, H., Lin, T.-B., Hsieh, M., Lai, C., Lee, A., Wang, H.-H., & Ho, Y. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108269 · Cited by 21 · see citing works
Kan, H., Peng, W., Wu, C., Wang, D., Lee, M. T., Lee, Y., Chu, T., & Ho, Y. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06250-1 · Cited by 18 · see citing works
Deyama, S., Aoki, S., Sugie, R., Fukuda, H., Shuto, S., Minami, M., & Kaneda, K. (2023) · Neurotherapeutics · doi:10.1007/s13311-022-01337-1 · Cited by 18 · see citing works
The PrLGlu→avBNSTGABA circuit rapidly modulates depression-like behaviors in male mice
Chen, J.-Y., Wu, K., Guo, M., Song, W., Huang, S.-T., & Zhang, Y.-M. (2023) · iScience · doi:10.1016/j.isci.2023.107878 · Cited by 18 · see citing works
Resolvins as potential candidates for the treatment of major depressive disorder
Deyama, S., Minami, M., & Kaneda, K. (2021) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2021.05.002 · Cited by 18 · see citing works
Camargo, A., Dalmagro, A. P., Wolin, I. A. V., Siteneski, A., Zeni, A. L. B., & Rodrigues, A. L. S. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2021.110371 · Cited by 17 · see citing works
Calder, A. E., Hase, A., & Hasler, G. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02830-z · Cited by 17 · see citing works
Role of group II metabotropic glutamate receptors in ketamine's antidepressant actions
Onisiforou, A., Georgiou, P., & Zanos, P. (2023) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2023.173531 · Cited by 12 · see citing works
Zhornitsky, S., Oliva, H. N. P., Jayne, L. A., Allsop, A. S., Kaye, A. P., Potenza, M. N., & Angarita, G. A. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1197890 · Cited by 15 · see citing works
Shao, J., Meng, L., Yang, Z., Yu, P., Song, L., Gao, Y., Gong, M., Meng, C., & Shi, H. (2020) · NeuroReport · doi:10.1097/wnr.0000000000001415 · Cited by 14 · see citing works
Banerjee, P., Donello, J., Hare, B. D., & Duman, R. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112706 · Cited by 13 · see citing works
Self-citationWidman, A. J., & McMahon, L. L. (2020) · Advances in pharmacology · doi:10.1016/bs.apha.2020.05.001 · Cited by 13 · see citing works
Novel rapid-acting antidepressants: molecular and cellular signaling mechanisms
Thomas, A. M., & Duman, R. S. (2017) · Neuronal Signaling · doi:10.1042/ns20170010 · Cited by 14 · see citing works
Self-citationResearch progress of non-monoamine antidepressants
Zhang, H., Wang, B., & Cao, X. (2021) · Stress and Brain · doi:10.26599/sab.2021.9060002 · Cited by 11 · see citing works
Yao, H., Wang, X., Chi, J., Chen, H., Liu, Y., Jiayi, Y., Yu, J., Ruan, Y., Xiang, X., Pi, J., et al. (2024) · Molecules · doi:10.3390/molecules29050964 · Cited by 11 · see citing works
Shen, M., Lv, D., Li, S., Zhang, Y., Wang, Z., Zhao, C., Chen, X., & Wang, C. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy324 · Cited by 10 · see citing works
Zheng, C., Qiao, Z., Hou, M. Z., Liu, N. N., Fu, B., Ding, R., Li, Y. Y., Wei, L. P., Liu, A. L., & Shen, H. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00186 · Cited by 10 · see citing works
Lu, C., Liu, X., Li, J., Huang, Y., Huang, X., Dai, G., & Wu, L. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00546 · Cited by 9 · see citing works
Li, C., Zhang, J., Liu, H., Yuan, H., Cai, J., Fogaça, M. V., & Zhang, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115137 · Cited by 8 · see citing works
Wohleb, E. S., Terwilliger, R. Z., Duman, C. H., & Duman, R. S. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.02.1119 · Cited by 9 · see citing works
Self-citationA novel NMDA receptor modulator: the antidepressant effect and mechanism of GW043
Tiliwaerde, M., Gao, N.-N., Yang, Y.-Q., & Jin, Z.-L. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14598 · Cited by 7 · see citing works
Zhang, W., Wang, W., Zhou, Y., & Wang, J. (2025) · Psychiatry Research · doi:10.1016/j.psychres.2025.116453 · Cited by 6 · see citing works
Zhu, Y., Qu, Y., Zhang, J., Hou, J., Fang, J., Shen, J., Xu, C. S., Huang, M., Qiao, H., & An, S.-C. (2021) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000660 · Cited by 6 · see citing works
Research Progress on NMDA Receptor Enhancement Drugs for the Treatment of Depressive Disorder
Liu, R., Liu, N., Ma, L., Liu, Y., Huang, Z., Peng, X., Zhuang, C., Niu, J., Yu, J., & Du, J. (2024) · CNS Drugs · doi:10.1007/s40263-024-01123-x · Cited by 5 · see citing works
Self-citationShin, J., Lee, J., Choi, J., Ahn, B.-T., Jang, S. C., You, S.-W., Koh, D.-Y., Maeng, S., & Cha, S.-Y. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/6897359 · Cited by 5 · see citing works
NMDAR modulators as rapid antidepressants: Converging and distinct signaling mechanisms
Lee, B., Pothula, S., & Duman, R. S. (2020) · Integrative Clinical Medicine · doi:10.15761/icm.1000173 · Cited by 5 · see citing works
Self-citationCheng, Z., Fan, J., Zhao, F., Su, J.-Y., Sun, Q., Cui, R.-J., & Li, B.-J. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.367928 · Cited by 5 · see citing works
Linkovski, O., Shen, H., Zwerling, J., Filippou-Frye, M., Jo, B., Cordell, E., Cooper, T. B., Simpson, H. B., Burch, R. M., Moskal, J. R., et al. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.17l11824 · Cited by 5 · see citing works
Self-citationRajagopal, L., Huang, M., He, W., Ryan, C., Elzokaky, A., Banerjee, P., & Meltzer, H. Y. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4042881 · Cited by 5 · see citing works
Neuroprotective roles of neurotrophic growth factors in mood disorders
Jiang, C., & Salton, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-814037-6.00010-0 · Cited by 5 · see citing works
Srivastava, J., Yadav, J., & Dubey, N. (2026) · Cognitive Neurodynamics · doi:10.1007/s11571-026-10446-y · Cited by 3 · see citing works
Neurochemical Signaling in Depression: Impact of Target-Based Pharmaceuticals
Sharma, B., & Khushboo (2022) · Current Drug Therapy · doi:10.2174/1574885517666220817122840 · Cited by 3 · see citing works
Coutellier, L. D., Musazzi, L., & Pavlovic, Z. M. (2022) · Springer eBooks · doi:10.1007/978-3-030-87480-3_4 · Cited by 2 · see citing works
(2R,6R)-Hydroxynorketamine, A Metabolite of Ketamine: The Antidepressant Actions and the Mechanisms
Fukumoto, K., & Duman, R. S. (2021) · Contemporary clinical neuroscience · doi:10.1007/978-3-030-79790-4_2 · Cited by 1 · see citing works
Self-citationWang, S., Zhou, X., Li, M., Zhang, C., Xu, H., He, J., Li, Z., Gu, Y., Gu, H., Tu, T., et al. (2025) · Advanced Science · doi:10.1002/advs.202509506 · Cited by 2 · see citing works
Vasilescu, A.-N., Pfeiffer, N., Terraneo, F., Riva, M. A., Lang, U. E., Inta, D., & Gass, P. (2022) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyac051 · Cited by 1 · see citing works
Özler, C., Özkan, E., Shomalizadeh, N., Kesibi, J., Sapancı, S., Akpunar, F., Uçar, E. A., & Özdemir, Y. (2025) · Experimental Brain Research · doi:10.1007/s00221-025-07085-w · Cited by 1 · see citing works
- Authors
- Liu, R.-J., Duman, C., Kato, T., Hare, B., Lopresto, D., Bang, E., Burgdorf, J., Moskal, J., Taylor, J., Aghajanian, G., & Duman, R. S.
- Affiliations
- Yale University (US)
- Sumitomo Dainippon Pharma (Japan) (JP)
- Northwestern University (US)
- Corresponding author
- Duman, Ronald S
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2016-09-16
- Volume
- 42
- Issue
- 6
- Pages
- 1231-1242
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC5437877
- OpenAlex
- W2518780615
- Cited by
- 105
- References
- 58
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 14 · 2021: 10 · 2020: 14 · 2019: 13 · 2018: 21 · 2017: 14
- FWCI
- 12.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- National Institute of Mental Health (R01MH093897, R37MH045481)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- ketamine, rapid-acting antidepressants, NMDA receptor modulators, mTORC1 signaling, rapamycin, medial prefrontal cortex, orexin, thalamocortical synapses, 5-HT2A receptor, impulsivity, attention, psychotomimetic side effects
- MeSH terms
- Animals, Antidepressive Agents, Behavior, Animal, Ketamine, Male, Mice, Inbred C57BL, Oligopeptides, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Prefrontal Cortex, Rats
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