Restoring Mood Balance in Depression: Ketamine Reverses Deficit in Dopamine-Dependent Synaptic Plasticity
Open accessAbstract
Background One of the most novel and exciting findings in major depressive disorder research over the last decade is the discovery of the fast-acting and long-lasting antidepressant effects of ketamine. Indeed, the therapeutic effects of classic antidepressants, such as selective serotonin reuptake inhibitors, require a month or longer to be expressed, with about a third of major depressive disorder patients resistant to treatment. Clinical studies have shown that a low dose of ketamine exhibits fast-acting relatively sustained antidepressant action, even in treatment-resistant patients. However, the mechanisms of ketamine action at a systems level remain unclear.Methods Wistar-Kyoto rats were exposed to inescapable, uncontrollable footshocks. To evaluate learned helplessness behavior, we used an active avoidance task in a shuttle box equipped with an electrical grid floor. After helplessness assessment, we performed in vivo electrophysiological recordings first from ventral tegmental area dopaminergic (DA) neurons and second from accumbens neurons responsive to fimbria stimulation. Ketamine was injected and tested on helpless behavior and electrophysiological recordings.Results We show that ketamine is able to restore the integrity of a network by acting on the DA system and restoring synaptic dysfunction observed in stress-induced depression. We show that part of the antidepressant effect of ketamine is via the DA system. Indeed, injection of ketamine restores a decreased dopamine neuron population activity, as well as synaptic plasticity (long-term potentiation) in the hippocampus-accumbens pathway, via, in part, activation of D1 receptors.Conclusions This work provides a unique systems perspective on the mechanisms of ketamine on a disrupted limbic system.
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In Wistar-Kyoto rats susceptible to learned helplessness, ketamine (5 mg/kg i.p.) reduced escape failures and latency when given 20 minutes or 24 hours before an active avoidance task.
“it was found that ketamine (5 mg/kg i.p.) rescued the learned helplessness phenotype, i.e. had fewer escape failures and reduced latency to escape, when administered 20 minutes or 24 hours prior to an active avoidance task (Belujon & Grace, 2014).”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Belujon & Grace, 2014
Given 24 hours earlier, ketamine restored both the number of spontaneously active dopamine neurons and their firing rate in helpless rats.
“When administered 24 hours prior to recordings, ketamine rescued a decrease in the number of spontaneously firing dopamine neurons and rescued a reduction in their firing rate in learned helpless rats.”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Belujon & Grace, 2014
The behavior matched lower VTA dopamine neuron activity in helpless rats, which ketamine reversed at 20 minutes.
“These behavioral effects corresponded to a reduction in dopamine neuron activity in the VTA in helpless rats which was rescued by ketamine 20 minutes post-treatment.”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Belujon & Grace, 2014
Ketamine, given 20 minutes before induction, restored LTP in the hippocampus-to-NAcc pathway of helpless rats.
“ketamine restored LTP induction which was otherwise impaired in helpless rats in the hippocampus to nucleus accumbens core (NAcc) pathway when administered 20 minutes prior to induction.”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Belujon & Grace, 2014
S-ketamine reverses elements of depressive-like symptoms in the WK model, including increasing mobility in the forced swim test, rescuing long-term potentiation and long-term spatial memory in the hippocampus, and attenuating dopamine-related synaptic deficits.
“S-ketamine has been reported to reverse elements of depressive-like symptoms in the WK model, for example, by increasing mobility in the FST, rescuing long-term potentiation in the hippocampus as well as long-term spatial memory, and attenuating dopamine-related synaptic deficits (Belujon and Grace, 2014; Aleksandrova et al., 2020).”
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 Belujon and Grace, 2014
Ketamine restores the ability to induce LTP in the hippocampus-accumbens pathway in stressed animals.
“Ketamine also restores the ability to induce LTP in the hippocampus-accumbens pathway in stressed animals [240].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [240]
Ketamine restores a stress-induced decrease in VTA dopaminergic cell firing.
“Ketamine restores a stress-induced decrease in VTA dopaminergic cell firing [240] and increases extracellular levels of dopamine in the nucleus accumbens [241].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [240]
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Cites
Kessler, R. C., Chiu, W. T., Demler, O., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.617 · Cited by 12,052 · see citing works
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
Responses to depression and their effects on the duration of depressive episodes
Nolen-Hoeksema, S. (1991) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.100.4.569 · Cited by 4,529 · 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
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
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
Dopamine neurons modulate neural encoding and expression of depression-related behaviour
Tye, K. M., Mirzabekov, J. J., Warden, M. R., Ferenczi, E. A., Tsai, H.-C., Finkelstein, J., Kim, S.-Y., Adhikari, A., Thompson, K. R., Andalman, A. S., et al. (2013) · Nature · doi:10.1038/nature11740 · Cited by 1,073 · see citing works
Regulation of firing of dopaminergic neurons and control of goal-directed behaviors
Grace, A. A., Floresco, S. B., Goto, Y., & Lodge, D. J. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.003 · Cited by 1,034 · see citing works
Self-citationGrace, A. A., & Bunney, B. S. (1983) · Neuroscience · doi:10.1016/0306-4522(83)90135-5 · Cited by 937 · see citing works
Self-citationO’Donnell, P., & Grace, A. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-05-03622.1995 · Cited by 760 · see citing works
Self-citationSafety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression
aan het Rot, M., Collins, K. A., Murrough, J. W., Perez, A. M., Reich, D. L., Charney, D. S., & Mathew, S. J. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.038 · Cited by 690 · see citing works
Synaptic plasticity and dynamic modulation of the postsynaptic membrane
Lüscher, C., Nicoll, R. A., Malenka, R. C., & Müller, D. (2000) · Nature Neuroscience · doi:10.1038/75714 · Cited by 641 · see citing works
Synaptic potentiation onto habenula neurons in the learned helplessness model of depression
Li, B., Piriz, J., Mirrione, M., Chung, C., Proulx, C. D., Schulz, D., Henn, F., & Malinow, R. (2011) · Nature · doi:10.1038/nature09742 · Cited by 634 · cited 3× · see citing works
“Learned Helplessness Paradigm In the LH paradigm (16,17), inescapable stress occurred on day 1 in one chamber of a two-chamber shuttle box (Med Associates, St.”
Dopamine and reward: The anhedonia hypothesis 30 years on
Wise, R. A. (2008) · Neurotoxicity Research · doi:10.1007/bf03033808 · Cited by 580 · see citing works
Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior
Goto, Y., & Grace, A. A. (2005) · Nature Neuroscience · doi:10.1038/nn1471 · Cited by 576 · see citing works
Self-citationNeural correlates of rumination in depression
Cooney, R. E., Joormann, J., Eugène, F., Dennis, E. L., & Gotlib, I. H. (2010) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/cabn.10.4.470 · Cited by 493 · cited 1× · see citing works
“In depressed patients, ruminative self-focus is associated with hyperactivity of limbic regions such as the medial prefrontal cortex, the amygdala, and the hippocampus (36).”
ΔFosB in brain reward circuits mediates resilience to stress and antidepressant responses
Vialou, V., Robison, A. J., LaPlant, Q. C., Covington, H. E., Dietz, D. M., Ohnishi, Y. N., Mouzon, E., Rush, A. J., Watts, E. L., Wallace, D. L., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2551 · Cited by 479 · see citing works
Lodge, D., & Grace, A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2847-07.2007 · Cited by 475 · see citing works
Self-citationGarcia, L. S. B., Comim, C. M., Valvassori, S. S., Réus, G. Z., Barbosa, L. M., Andreazza, A. C., Stertz, L., Fries, G. R., Gavioli, E. C., Kapczinski, F., et al. (2008) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2007.07.027 · Cited by 454 · see citing works
Are you or aren’t you? Challenges associated with physiologically identifying dopamine neurons
Ungless, M. A., & Grace, A. A. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.02.003 · Cited by 431 · see citing works
Self-citationSelective activation of dopamine transmission in the shell of the nucleus accumbens by stress
Kalivas, P. W., & Duffy, P. (1995) · Brain Research · doi:10.1016/0006-8993(95)00013-g · Cited by 395 · see citing works
Koike, H., Iijima, M., & Chaki, S. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.05.035 · Cited by 346 · see citing works
Papageorgiou, C., & Adrian Wells, A. (2001) · Behavior Therapy · doi:10.1016/s0005-7894(01)80041-1 · Cited by 318 · see citing works
Lodge, D. J., & Grace, A. A. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300963 · Cited by 280 · see citing works
Self-citationFloresco, S., Blaha, C. D., Yang, C. R., & Phillips, A. G. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-08-02851.2001 · Cited by 242 · see citing works
Amygdala-Ventral Pallidum Pathway Decreases Dopamine Activity After Chronic Mild Stress in Rats
Chang, C.-H., & Grace, A. A. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.09.020 · Cited by 239 · see citing works
Self-citationRole of the ventral subiculum in stress integration
Herman, J. P., & Mueller, N. K. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.05.035 · Cited by 235 · see citing works
Synaptic plasticity and phosphorylation
Lee, H. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.06.003 · Cited by 215 · see citing works
Blaha, C. D., Yang, C. R., Floresco, S., Barr, A. M., & Phillips, A. G. (1997) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1997.tb01441.x · Cited by 207 · see citing works
Kissin, I., Bright, C. A., & Bradley, E. L. (2000) · Anesthesia & Analgesia · doi:10.1097/00000539-200012000-00035 · Cited by 200 · see citing works
Mulder, A. B., Hodenpijl, M. G., & Lopes, F. H. D. S. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-13-05095.1998 · Cited by 173 · see citing works
Tizabi, Y., Bhatti, B. H., Manaye, K. F., Das, J. R., & Akinfiresoye, L. R. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.03.052 · Cited by 172 · see citing works
Gill, K., Lodge, D., Cook, J., Aras, S., & Grace, A. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.76 · Cited by 170 · see citing works
Self-citationDonahue, R. J., Muschamp, J. W., Russo, S. J., Nestler, E. J., & Carlezon, W. A. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.12.014 · Cited by 161 · see citing works
Non-competitive antagonists are potent activators of ventral tegmental A10 dopamine neurons
French, E. D., & Ceci, A. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90823-r · Cited by 155 · see citing works
Maier, S. F. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01095-7 · Cited by 135 · see citing works
Dwyer, J. M., & Duman, R. S. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.11.011 · Cited by 134 · see citing works
Valenti, O., Gill, K. M., & Grace, A. A. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08038.x · Cited by 131 · see citing works
Self-citationLodge, D. J., & Grace, A. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1582-08.2008 · Cited by 127 · see citing works
Self-citationStress-Induced Changes in Nucleus Accumbens Glutamate Synaptic Plasticity
Campioni, M. R., Xu, M., & McGehee, D. S. (2009) · Journal of Neurophysiology · doi:10.1152/jn.91111.2008 · Cited by 115 · see citing works
Liu, J., & Moghaddam, B. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10607-1 · Cited by 89 · see citing works
Critical Role of the Prefrontal Cortex in the Regulation of Hippocampus–Accumbens Information Flow
Belujon, P., & Grace, A. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2200-08.2008 · Cited by 78 · see citing works
Self-citationStock differences in the susceptibility of rats to learned helplessness training
Wieland, S., Boren, J. L., Consroe, P. F., & Martin, A. (1986) · Life Sciences · doi:10.1016/0024-3205(86)90376-0 · Cited by 72 · see citing works
Rumination and distraction in major depression: assessing response to pharmacological treatment
Bagby, R. M., Rector, N. A., Segal, Z. V., Joffe, R. T., LEVITT, A. J., Kennedy, S. H., & Levitan, R. D. (1999) · Journal of Affective Disorders · doi:10.1016/s0165-0327(99)00015-4 · Cited by 58 · see citing works
Belujon, P., Patton, M. H., & Grace, A. A. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs380 · Cited by 43 · see citing works
Self-citationReduced sensitivity to sucrose in rats bred for helplessness: a study using the matching law
Sanchis‐Segura, C., Spanagel, R., Henn, F. A., & Vollmayr, B. (2005) · Behavioural Pharmacology · doi:10.1097/01.fbp.0000171772.61669.6f · Cited by 42 · see citing works
Valentine, G. W., Dow, A. L., Banasr, M., Pittman, B. P., & Duman, R. S. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1239-z · Cited by 32 · see citing works
D1–NMDA receptor interactions in the rat nucleus accumbens change during adolescence
Huppé‐Gourgues, F., & O’Donnell, P. (2012) · Synapse · doi:10.1002/syn.21544 · Cited by 31 · see citing works
Serotonergic Modulation of Learned Helplessness
Petty, F., Kramer, G. L., & WU, J. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb48324.x · Cited by 30 · see citing works
Kessal, K., Chessel, A., Spennato, G., & Garcia, R. (2005) · Synapse · doi:10.1002/syn.20154 · Cited by 16 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [53]Paxinos G Watson C 1996 The Rat Brain in Stereotatic Coordinates Academic Press San Diego
Cited by
Sorted by citations
Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression
Grace, A. A. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.57 · Cited by 1,166 · see citing works
Self-citationDopamine system dysregulation in major depressive disorders
Belujon, P., & Grace, A. A. (2017) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx056 · Cited by 754 · see citing works
Self-citationThe Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex
Liu, W., Ge, T., Leng, Y., Pan, Z., Fan, J., Yang, W., & Cui, R. (2017) · Neural Plasticity · doi:10.1155/2017/6871089 · Cited by 640 · see citing works
Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression.
Newport, D. J., Carpenter, L. L., McDonald, W. M., Potash, J. B., Tohen, M., Nemeroff, C. B., & The APA Council of Research Task Force on Novel Biomarkers and Treatments (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15040465 · Cited by 598 · see citing works
Pathogenesis of depression: Insights from human and rodent studies
Ménard, C., Hodes, G. E., & Russo, S. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.053 · Cited by 593 · see citing works
Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression
Bagot, R. C., Parise, E. M., Peña, C. J., Zhang, H.-X., Maze, I., Chaudhury, D., Persaud, B., Cachope, R., Bolaños-Guzmán, C. A., Cheer, J. F., et al. (2015) · Nature Communications · doi:10.1038/ncomms8062 · Cited by 491 · see citing works
Hashimoto, K. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12902 · Cited by 335 · see citing works
An integrative perspective on the role of dopamine in schizophrenia
Maia, T. V., & Frank, M. J. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.021 · Cited by 293 · see citing works
An excitatory synapse hypothesis of depression
Thompson, S. M., Kallarackal, A. J., Kvarta, M. D., Van Dyke, A. M., LeGates, T. A., & Cai, X. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.03.003 · Cited by 265 · see citing works
Reinforcement learning in depression: a review of computational research
Chen, C., Takahashi, T., Nakagawa, S., Inoue, T., & Kusumi, I. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.005 · Cited by 233 · see citing works
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Inserra, A., De Gregorio, D., & Gobbi, G. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000056 · Cited by 232 · see citing works
The stressed synapse 2.0: pathophysiological mechanisms in stress-related neuropsychiatric disorders
Sanacora, G., Yan, Z., & Popoli, M. (2022) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00540-x · Cited by 197 · see citing works
Convergent 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
Mechanisms of ketamine and its metabolites as antidepressants
Hess, E. M., Riggs, L. M., Michaelides, M., & Gould, T. D. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114892 · Cited by 169 · see citing works
Glutamatergic 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
Cavalleri, L., Merlo Pich, E., Millan, M. J., Chiamulera, C., Kunath, T., Spano, P. F., & Collo, G. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.241 · Cited by 156 · see citing works
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
Fischell, J., Van Dyke, A. M., Kvarta, M. D., LeGates, T. A., & Thompson, S. M. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.112 · Cited by 122 · see citing works
The Nucleus Accumbens and Ketamine Treatment in Major Depressive Disorder
Abdallah, C. G., Jackowski, A., Salas, R., Gupta, S., Sato, J. R., Mao, X., Coplan, J. D., Shungu, D. C., & Mathew, S. J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.49 · Cited by 123 · see citing works
Can, A., Zanos, P., Moaddel, R., Kang, H. J., Dossou, K. S. S., Wainer, I. W., Cheer, J. F., Frost, D. O., Huang, X.-P., & Gould, T. D. (2016) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.235838 · Cited by 115 · see citing works
Aleksandrova, L. R., Wang, Y. T., & Phillips, A. G. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.07.007 · Cited by 114 · see citing works
Ketamine modulates fronto-striatal circuitry in depressed and healthy individuals
Mkrtchian, A., Evans, J. W., Kraus, C., Yuan, P., Kadriu, B., Nugent, A. C., Roiser, J. P., & Zarate, C. A. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00878-1 · Cited by 110 · see citing works
Murrough, J. W., Collins, K. A., Fields, J., DeWilde, K. E., Phillips, M. L., Mathew, S. J., Wong, E., Tang, C. Y., Charney, D. S., & Iosifescu, D. V. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.10 · Cited by 109 · see citing works
Witkin, J. M., Monn, J. A., Schoepp, D. D., Li, X., Overshiner, C., Mitchell, S. N., Carter, G., Johnson, B., Rasmussen, K., & Rorick-Kehn, L. M. (2016) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.233627 · Cited by 105 · see citing works
Rincón-Cortés, M., & Grace, A. A. (2017) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx048 · Cited by 98 · see citing works
Self-citationMoreines, J. L., Owrutsky, Z. L., & Grace, A. A. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.249 · Cited by 93 · see citing works
Self-citationGomes, F. V., Zhu, X., & Grace, A. A. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0514-1 · Cited by 91 · see citing works
Self-citationAleksandrova, L. R., Wang, Y. T., & Phillips, A. G. (2020) · Molecular Brain · doi:10.1186/s13041-020-00627-z · Cited by 85 · see citing works
El Iskandrani, K. S., Oosterhof, C. A., El Mansari, M., & Blier, P. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881115573809 · Cited by 75 · see citing works
mGlu2/3 Receptor Antagonists as Novel Antidepressants
Chaki, S. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.03.008 · Cited by 73 · see citing works
Picard, N., Takesian, A. E., Fagiolini, M., & Hensch, T. K. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0341-9 · Cited by 71 · see citing works
Millard, S. J., Weston-Green, K., & Newell, K. A. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109908 · Cited by 62 · see citing works
Li, D.-J., Wang, F.-C., Chu, C.-S., Chen, T.-Y., Tang, C.-H., Yang, W.-C., Chow, P. C.-K., Wu, C.-K., Tseng, P.-T., & Lin, P.-Y. (2017) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2016.11.008 · Cited by 51 · see citing works
Targeting metaplasticity mechanisms to promote sustained antidepressant actions
Brown, K. A., & Gould, T. D. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02397-1 · Cited by 49 · 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
WHITHER KETAMINE AS AN ANTIDEPRESSANT: PANACEA OR TOXIN?: Editorial
Newport, D. J., Schatzberg, A. F., & Nemeroff, C. B. (2016) · Depression and Anxiety · doi:10.1002/da.22535 · Cited by 30 · see citing works
Cai, M., Zhu, Y., Shanley, M. R., Morel, C., Ku, S. M., Zhang, H., Shen, Y., Friedman, A. K., & Han, M.-H. (2023) · Neurobiology of Stress · doi:10.1016/j.ynstr.2023.100565 · Cited by 18 · see citing works
Moreines, J. L., Owrutsky, Z. L., Gagnon, K. G., & Grace, A. A. (2017) · Translational Psychiatry · doi:10.1038/s41398-017-0039-9 · Cited by 17 · see citing works
Self-citationBarnett (2024) · doi:10.1089/psymed.2023.0010 · Cited by 13 · 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
- Belujon, P., & Grace, A. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Belujon, Pauline
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 76
- Issue
- 12
- Pages
- 927-936
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4223010
- OpenAlex
- W1980938183
- Cited by
- 225
- References
- 53
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 14 · 2023: 15 · 2022: 14 · 2021: 18 · 2020: 30 · 2019: 25 · 2018: 16 · 2017: 21 · 2016: 20 · 2015: 21 · 2014: 2 · 2013: 1
- FWCI
- 15.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- United States Public Health Service (MH57440 and MH191180)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ketamine, major depressive disorder, antidepressant mechanism, dopamine, synaptic plasticity, long-term potentiation, ventral tegmental area, accumbens, dopamine D1 receptor, learned helplessness, stress-induced depression, limbic system, treatment-resistant depression
- MeSH terms
- Action Potentials, Animals, Antidepressive Agents, Benzazepines, Brain, Depression, Disease Models, Animal, Electroshock, Helplessness, Learned, Ketamine, Male, Neural Pathways, Rats, Inbred WKY, Reaction Time, Time Factors, Long-Term Potentiation, Dopamine Agonists, Rats, Dopaminergic Neurons
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