GSK-3 inhibition potentiates the synaptogenic and antidepressant-like effects of subthreshold doses of ketamine
Open accessAbstract
A single dose of the short-acting NMDA antagonist ketamine produces rapid and prolonged antidepressant effects in treatment-resistant patients with major depressive disorder (MDD), which are thought to occur via restoration of synaptic connectivity. However, acute dissociative side effects and eventual fading of antidepressant effects limit widespread clinical use of ketamine. Recent studies in medial prefrontal cortex (mPFC) show that the synaptogenic and antidepressant-like effects of a single standard dose of ketamine in rodents are dependent upon activation of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway together with inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3), which relieves its inhibitory in influence on mTOR. Here, we found that the synaptogenic and antidepressant-like effects of a single otherwise subthreshold dose of ketamine were potentiated when given together with a single dose of lithium chloride (a nonselective GSK-3 inhibitor) or a preferential GSK-3β inhibitor; these effects included rapid activation of the mTORC1 signaling pathway, increased inhibitory phosphorylation of GSK-3β, increased synaptic spine density/diameter, increased excitatory postsynaptic currents in mPFC layer V pyramidal neurons, and antidepressant responses that persist for up to 1 week in the forced-swim test model of depression. The results demonstrate that low, subthreshold doses of ketamine combined with lithium or a selective GSK-3 inhibitor are equivalent to higher doses of ketamine, indicating the pivotal role of the GSK-3 pathway in modulating the synaptogenic and antidepressant responses to ketamine. The possible mitigation by GSK-3 inhibitors of the eventual fading of ketamine's antidepressant effects remains to be explored.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Multiple studies reported ketamine increasing dendritic spine density within 12-24 h.
“Multiple studies have reported similar occurrences with ketamine increasing dendritic spine density within 12–24 h of administration (Li et al., 2010; Liu et al., 2013; Moda-Sava et al., 2019).”
From A single subanaesthetic dose of the rapid-acting antidepressant S-ketamine raises presynaptic SV2A density in limbic regions of the Wistar Kyoto rat model of depression (2024) · cites this paper as Liu et al., 2013
Currently MDD is typically treated with monoamine neurotransmission drugs, but these drugs can take weeks to months to produce therapeutic response, have limited efficacy, and low rates of full remission.
“Currently, MDD is typically treated with drugs that influence monoamine neurotransmission, but large-scale clinical trials (i.e., STAR*D) show that these drugs can take weeks to months to produce a therapeutic response, have limited efficacy, and result in low rates of full remission (24).”
From Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation (2019) · cites this paper as [24]
A 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 [24]
Heterozygous deletion of BDNF decreases spine density and dendrite length of hippocampal and PFC neurons, decreases hippocampal volume, and occludes the effects of chronic stress.
“Heterozygous deletion of BDNF also decreases spine density and dendrite length of hippocampal and PFC neurons, decreases hippocampal volume, and occludes the effects of chronic stress39,40.”
From Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants (2016) · cites this paper as [39]
mTORC1 activation and phosphorylation of GSK-3 might be a convergent mechanism involved in ketamine's antidepressant actions.
“Administration of combined subthreshold doses of ketamine and lithium (a non-selective GSK-3 inhibitor), or a selective GSK-3 inhibitor, induced an activation of the mTORC1 signaling pathway, phosphorylation of GSK-3, synaptoneurogenesis and enhanced antidepressant actions 187, suggesting that mTORC1 activation and phosphorylation of GSK-3 might be a convergent mechanism involved in ketamine’s ant”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [187]
Administration of combined subthreshold doses of ketamine and lithium (a non-selective GSK-3 inhibitor), or a selective GSK-3 inhibitor, induces an activation of the mTORC1 signaling pathway, phosphorylation of GSK-3, synaptoneurogenesis and enhanced antidepressant actions.
“Administration of combined subthreshold doses of ketamine and lithium (a non-selective GSK-3 inhibitor), or a selective GSK-3 inhibitor, induced an activation of the mTORC1 signaling pathway, phosphorylation of GSK-3, synaptoneurogenesis and enhanced antidepressant actions 187, suggesting that mTORC1 activation and phosphorylation of GSK-3 might be a convergent mechanism involved in ketamine’s ant”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [187]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941 · 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
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., Charney, D. S., & Manji, H. K. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.856 · Cited by 3,766 · 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-citationSynaptic Dysfunction in Depression: Potential Therapeutic Targets
Duman, R. S., & Aghajanian, G. K. (2012) · Science · doi:10.1126/science.1222939 · Cited by 1,651 · cited 1× · see citing works
“Postmortem and genetic studies suggest that basal GSK-3 activity may be increased in mood disorders (Jope, 2011), possibly contributing to deficits in synaptic connectivity that eventually develop in MDD (Duman and Aghajanian, 2012).”
BackgroundSelf-citationNew approaches to antidepressant drug discovery: beyond monoamines
Berton, O., & Nestler, E. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1846 · Cited by 1,589 · 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
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-citationDiazgranados, N., Ibrahim, L., Brutsche, N. E., Newberg, A., Kronstein, P., Khalife, S., Kammerer, W. A., Quezado, Z., Luckenbaugh, D. A., Salvadore, G., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.90 · Cited by 963 · see citing works
Long-term depression in the CNS
Collingridge, G. L., Peineau, S., Howland, J. G., & Wang, Y. T. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2867 · Cited by 926 · see citing works
Zarate, C. A., Brutsche, N. E., Ibrahim, L., Franco-Chaves, J., Diazgranados, N., Cravchik, A., Selter, J., Marquardt, C. A., Liberty, V., & Luckenbaugh, D. A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.12.010 · Cited by 811 · see citing works
Decreased expression of synapse-related genes and loss of synapses in major depressive disorder
Kang, H. J., Voleti, B., Hajszan, T., Rajkowska, G., Stockmeier, C. A., Licznerski, P., Lepack, A., Majik, M. S., Jeong, L. S., Banasr, M., et al. (2012) · Nature Medicine · doi:10.1038/nm.2886 · Cited by 808 · see citing works
Self-citationGSK-3: Functional Insights from Cell Biology and Animal Models
Kaidanovich‐Beilin, O., & Woodgett, J. R. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00040 · Cited by 487 · 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
Glycogen Synthase Kinase-3: a Putative Molecular Target for Lithium Mimetic Drugs
Gould, T. D., & Manji, H. K. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300731 · Cited by 377 · 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-citationGould, T. D., Einat, H., Bhat, R. V., & Manji, H. K. (2004) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145704004535 · Cited by 314 · see citing works
Fekadu, A., Wooderson, S. C., Markopoulo, K., Donaldson, C., Papadopoulos, A. S., & Cleare, A. J. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.10.014 · Cited by 299 · see citing works
Dendritic spine formation and stabilization
Yoshihara, Y., De Roo, M., & Muller, D. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.05.013 · Cited by 292 · see citing works
Beurel, E., Song, L., & Jope, R. S. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.47 · Cited by 288 · see citing works
Kaidanovich‐Beilin, O., Milman, A., Weizman, A., Pick, C. G., & Eldar-Finkelman, H. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.01.008 · Cited by 276 · see citing works
Inhibition of GSK3 by lithium, from single molecules to signaling networks
Freland, L., & Beaulieu, J. (2012) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2012.00014 · Cited by 269 · see citing works
Novel Insights into Lithium’s Mechanism of Action: Neurotrophic and Neuroprotective Effects
Quiroz, J. A., Machado‐Vieira, R., Zarate, C. A., & Manji, H. K. (2010) · Neuropsychobiology · doi:10.1159/000314310 · Cited by 225 · see citing works
Polter, A., Beurel, E., Yang, S., Garner, R., Song, L., Miller, C. A., Sweatt, J. D., McMahon, L., Bartolucci, A. A., Li, X., et al. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.43 · Cited by 225 · see citing works
A pivotal role of GSK-3 in synaptic plasticity
Bradley, C. A., Peineau, S., Taghibiglou, C., Nicolas, C. S., Whitcomb, D. J., Bortolotto, Z. A., Kaang, B., Cho, K., Wang, Y. T., & Collingridge, G. L. (2012) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2012.00013 · Cited by 189 · see citing works
Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders
Jope, R. S. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00016 · Cited by 174 · see citing works
Treatment-resistant depression.
Little, A. A. (2009) · PubMed · Cited by 151 · see citing works
Lambe, E. K., & Aghajanian, G. K. (2003) · Neuron · doi:10.1016/s0896-6273(03)00598-1 · Cited by 127 · see citing works
Self-citationMa, X., Dang, Y., Jia, M., Ma, R., Wang, F., Wu, J., Gao, C., & Hashimoto, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056053 · Cited by 114 · see citing works
Ghasemi, M., Raza, M., & Dehpour, A. R. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881109104845 · Cited by 91 · see citing works
Treatment-resistant depression: recent developments and future directions
Mathew, S. J. (2008) · Depression and Anxiety · doi:10.1002/da.20540 · Cited by 51 · see citing works
Deguil, J., Pérault‐Pochat, M. C., Chavant, F., Lafay‐Chebassier, C., Fauconneau, B., & Pain, S. (2008) · Toxicology Letters · doi:10.1016/j.toxlet.2008.08.012 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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-citationMechanisms 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
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
Abdallah, 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-citationMiller, 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
Hashimoto, K. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12902 · Cited by 335 · see citing works
Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants
Browne, C. A., & Lucki, I. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00161 · Cited by 285 · see citing works
Fuchikami, 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-citationLally, N., Nugent, A. C., Luckenbaugh, D. A., Ameli, R., Roiser, J. P., & Zarate, C. A. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.105 · Cited by 271 · see citing works
Spine synapse remodeling in the pathophysiology and treatment of depression
Duman, C. H., & Duman, R. S. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.01.022 · Cited by 257 · see citing works
Self-citationDuman, R. S. (2014) · Depression and Anxiety · doi:10.1002/da.22227 · Cited by 213 · see citing works
Self-citationKETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah, C. G., Adams, T. G., Kelmendi, B., Esterlis, I., Sanacora, G., & Krystal, J. H. (2016) · Depression and Anxiety · doi:10.1002/da.22501 · Cited by 206 · see citing works
Iadarola, N. D., Niciu, M. J., Richards, E. M., Vande Voort, J. L., Ballard, E. D., Lundin, N. B., Nugent, A. C., Machado-Vieira, R., & Zarate, C. A. (2015) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622315579059 · Cited by 201 · see citing works
Pham, T. H., & Gardier, A. M. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.017 · Cited by 186 · 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-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-citationHippocampal MicroRNA-124 Enhances Chronic Stress Resilience in Mice
Higuchi, F., Uchida, S., Yamagata, H., Abe-Higuchi, N., Hobara, T., Hara, K., Kobayashi, A., Shintaku, T., Itoh, Y., Suzuki, T., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0319-16.2016 · Cited by 158 · see citing works
Antidepressant actions of ketamine: from molecular mechanisms to clinical practice
Monteggia, L. M., & Zarate, C. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.12.004 · Cited by 149 · see citing works
GABAergic Control of Depression-Related Brain States
Luscher, B., & Fuchs, T. (2015) · Advances in Pharmacology · doi:10.1016/bs.apha.2014.11.003 · Cited by 149 · see citing works
Phoumthipphavong, V., Barthas, F., Hassett, S., & Kwan, A. C. (2016) · eneuro · doi:10.1523/eneuro.0133-15.2016 · Cited by 132 · see citing works
Orozco-Solis, R., Montellier, E., Aguilar-Arnal, L., Sato, S., Vawter, M. P., Bunney, B. G., Bunney, W. E., & Sassone-Corsi, P. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.02.1176 · Cited by 119 · see citing works
Liu, R.-J., Duman, C., Kato, T., Hare, B., Lopresto, D., Bang, E., Burgdorf, J., Moskal, J., Taylor, J., Aghajanian, G., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.202 · Cited by 105 · see citing works
Self-citationGriebel, G., Stemmelin, J., Lopez-Grancha, M., Boulay, D., Boquet, G., Slowinski, F., Pichat, P., Beeské, S., Tanaka, S., Mori, A., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-54557-5 · Cited by 97 · see citing works
Brand, S., Moller, M., & Harvey, B. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150307004545 · Cited by 95 · see citing works
Neuroplasticity and the next wave of antidepressant strategies
Hayley, S., & Litteljohn, D. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00218 · Cited by 92 · see citing works
Sestrin 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-citationNg, L. H. L., Huang, Y., Han, L., Chang, R. C.-C., Chan, Y. S., & Lai, C. S. W. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0321-5 · Cited by 82 · see citing works
GSK3β: a master player in depressive disorder pathogenesis and treatment responsiveness
Duda, P., Hajka, D., Wójcicka, O., Rakus, D., & Gizak, A. (2020) · Cells · doi:10.3390/cells9030727 · Cited by 84 · see citing works
Datta, D., & Arnsten, A. (2019) · Brain Sciences · doi:10.3390/brainsci9050113 · Cited by 78 · see citing works
Beurel, E., Grieco, S. F., Amadei, C., Downey, K., & Jope, R. S. (2016) · Bipolar Disorders · doi:10.1111/bdi.12436 · Cited by 76 · see citing works
Kang, M. J. Y., Hawken, E., & Vazquez, G. H. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.860882 · Cited by 77 · 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-citationCosti, S., Soleimani, L., Glasgow, A., Brallier, J., Spivack, J., Schwartz, J., Levitch, C. F., Richards, S., Hoch, M., Stade, E. C., et al. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0365-0 · Cited by 56 · see citing works
Siegel, J. S., Palanca, B. J. A., Ances, B. M., Kharasch, E. D., Schweiger, J. A., Yingling, M. D., Snyder, A. Z., Nicol, G. E., Lenze, E. J., & Farber, N. B. (2021) · Psychopharmacology · doi:10.1007/s00213-021-05762-6 · Cited by 50 · see citing works
Rantamäki, T., & Kohtala, S. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018697 · Cited by 45 · see citing works
Mingardi, J., La Via, L., Tornese, P., Carini, G., Trontti, K., Seguini, M., Tardito, D., Bono, F., Fiorentini, C., Elia, L., et al. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100381 · Cited by 36 · see citing works
Abdallah, C., Averill, L. A., Gueorguieva, R., Goktas, S., Purohit, P., Ranganathan, M., D'Souza, D. C., Formica, R., Southwick, S. M., Duman, R. S., et al. (2018) · doi:10.1101/500959 · Cited by 30 · see citing works
Self-citationOpler, L. A., Opler, M. G. A., & Arnsten, A. F. T. (2016) · CNS Spectrums · doi:10.1017/s1092852914000686 · Cited by 28 · see citing works
Ren, L. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2023.110910 · Cited by 23 · see citing works
Bærentzen, S. L., Waszkiewicz, A. L., Thomsen, M., Knudsen, C., Elfving, B., & Landau, A. M. (2024) · Neuroscience Applied · doi:10.1016/j.nsa.2024.104079 · Cited by 7 · see citing works
- Authors
- Liu, R.-J., Fuchikami, M., Dwyer, J. M., Lepack, A. E., Duman, R. S., & Aghajanian, G. K.
- Affiliations
- Yale University (US)
- Corresponding author
- Aghajanian, George K
- Venue
- Neuropsychopharmacology
- Published
- 2013-05-17
- Volume
- 38
- Issue
- 11
- Pages
- 2268-2277
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3773678
- OpenAlex
- W2051187163
- Cited by
- 256
- References
- 32
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 13 · 2023: 18 · 2022: 21 · 2021: 22 · 2020: 25 · 2019: 27 · 2018: 17 · 2017: 18 · 2016: 28 · 2015: 23 · 2014: 14 · 2013: 7
- FWCI
- 17.90
- 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
- National Institutes of Health
- National Institute of Mental Health (MH093897, R01MH093897)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- ketamine, glycogen synthase kinase-3, GSK3 inhibition, lithium chloride, mTORC1 signaling, antidepressant effects, synaptogenesis, medial prefrontal cortex, excitatory postsynaptic currents, major depressive disorder, forced swim test
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Antidepressive Agents, Dose-Response Relationship, Drug, Drug Synergism, Indoles, Ketamine, Male, Maleimides, Phosphorylation, Synapses, Signal Transduction, Prefrontal Cortex, Lithium Chloride, Excitatory Postsynaptic Potentials, Glycogen Synthase Kinase 3, Immobility Response, Tonic, Multiprotein Complexes, Dendritic Spines, Rats, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
