Negative Allosteric Modulation of Gamma-Aminobutyric Acid A Receptors at α5 Subunit–Containing Benzodiazepine Sites Reverses Stress-Induced Anhedonia and Weakened Synaptic Function in Mice
Open accessAbstract
Background Abnormal reward processing, typically anhedonia, is a hallmark of human depression and is accompanied by altered functional connectivity in reward circuits. Negative allosteric modulators of GABA A (gamma-aminobutyric acid A) receptors (GABA-NAMs) have rapid antidepressant-like properties in rodents and exert few adverse effects, but molecular targets underlying their behavioral and synaptic effects remain undetermined. We hypothesized that GABA-NAMs act at the benzodiazepine site of GABA A receptors containing α5 subunits to increase gamma oscillatory activity, strengthen synapses in reward circuits, and reverse anhedonia.Methods Anhedonia was induced by chronic stress in male mice and assayed by preferences for sucrose and female urine (n = 5-7 mice/group). Hippocampal slices were then prepared for electrophysiological recording (n = 1-6 slices/mouse, 4-6 mice/group). Electroencephalography power was quantified in response to GABA-NAM and ketamine administration (n = 7-9 mice/group).Results Chronic stress reduced sucrose and female urine preferences and hippocampal temporoammonic-CA1 synaptic strength. A peripheral injection of the GABA-NAM MRK-016 restored hedonic behavior and AMPA-to-NMDA ratios in wild-type mice. These actions were prevented by pretreatment with the benzodiazepine site antagonist flumazenil. MRK-016 administration increased gamma power over the prefrontal cortex in wild-type mice but not α5 knockout mice, whereas ketamine promoted gamma power in both genotypes. Hedonic behavior and AMPA-to-NMDA ratios were only restored by MRK-016 in stressed wild-type mice but not α5 knockout mice.Conclusions α5-Selective GABA-NAMs exert rapid anti-anhedonic actions and restore the strength of synapses in reward regions by acting at the benzodiazepine site of α5-containing GABA A receptors. These results encourage human studies using GABA-NAMs to treat depression by providing readily translatable measures of target engagement.
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Ketamine and GABA A receptor negative allosteric modulators promote gamma oscillations in the prefrontal cortex at doses that reverse chronic stress behavioral consequences.
“Indeed, ketamine and GABA A receptor negative allosteric modulators share an ability to promote gamma oscillations in the PFC at doses that reverse the behavioral consequences of chronic stress [152,153].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [152]
Subsequent preclinical experiments supported the hypothesis that negative allosteric modulators of GABA A receptors containing alpha5 subunits would produce a ketamine-like rapid antidepressant response.
“Subsequent preclinical experiments supported this hypothesis [152,273].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [152]
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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
A Neurotrophic Model for Stress-Related Mood Disorders
Duman, R. S., & Monteggia, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.013 · Cited by 3,375 · see citing works
Resting-state connectivity biomarkers define neurophysiological subtypes of depression
Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., Fetcho, R. N., Zebley, B., Oathes, D. J., Etkin, A., et al. (2017) · Nature Medicine · doi:10.1038/nm.4246 · Cited by 2,170 · see citing works
Hippocampal atrophy in recurrent major depression
Sheline, Y. I., Wang, P. W., Gado, M. H., Csernansky, J. G., & Vannier, M. W. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.3908 · Cited by 1,932 · 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
NMDAR inhibition-independent antidepressant actions of ketamine metabolites
Zanos, P., Moaddel, R., Morris, P. J., Georgiou, P., Fischell, J., Elmer, G. I., Alkondon, M., Yuan, P., Pribut, H. J., Singh, N. S., et al. (2016) · Nature · doi:10.1038/nature17998 · Cited by 1,609 · see citing works
Self-citationFritschy, J., & Mohler, H. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903590111 · Cited by 1,244 · 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
Turning on and off recurrent balanced cortical activity
Shu, Y., Hasenstaub, A., & McCormick, D. A. (2003) · Nature · doi:10.1038/nature01616 · Cited by 1,054 · see citing works
The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death
Sapolsky, R. M. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00971-9 · Cited by 699 · see citing works
Gaynes, B. N., Warden, D., Trivedi, M. H., Wisniewski, S. R., Fava, M., & Rush, A. J. (2009) · Psychiatric Services · doi:10.1176/ps.2009.60.11.1439 · Cited by 661 · see citing works
Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation
Moda-Sava, R. N., Murdock, M. H., Parekh, P. K., Fetcho, R. N., Huang, B. S., Huynh, T. N., Witztum, J., Shaver, D. C., Rosenthal, D. L., Alway, E. J., et al. (2019) · Science · doi:10.1126/science.aat8078 · Cited by 643 · see citing works
Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: Comparison of stressors
Magarin˜os, A. M., & McEwen, B. S. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00256-i · Cited by 571 · see citing works
Yuen, E. Y., Wei, J., Liu, W., Zhong, P., Li, X., & Yan, Z. (2012) · Neuron · doi:10.1016/j.neuron.2011.12.033 · Cited by 558 · see citing works
Brain structure alterations in depression: Psychoradiological evidence
Zhang, F., Peng, W. J., Sweeney, J. A., Jia, Z., & Gong, Q. (2018) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12835 · Cited by 507 · see citing works
Agonist and antagonist benzodiazepine receptor interaction in vitro
Möhler, H., & Richards, J. G. (1981) · Nature · doi:10.1038/294763a0 · Cited by 381 · see citing works
Billings, A. G., Cronkite, R. C., & Moos, R. H. (1983) · Journal of Abnormal Psychology · doi:10.1037//0021-843x.92.2.119 · Cited by 362 · see citing works
Silva-Gómez, A. B., Rojas, D., Juárez, I., & Flores, G. (2003) · Brain Research · doi:10.1016/s0006-8993(03)03042-7 · Cited by 336 · see citing works
Suicidal Behaviour in Mood Disorders—Who, When, and Why?
Isometsä, E. T. (2014) · The Canadian Journal of Psychiatry · doi:10.1177/070674371405900303 · Cited by 311 · see citing works
Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses
LeGates, T. A., Kvarta, M. D., Tooley, J. R., Francis, T. C., Lobo, M. K., Creed, M. C., & Thompson, S. M. (2018) · Nature · doi:10.1038/s41586-018-0740-8 · Cited by 290 · see citing works
Self-citationTripp, A., Oh, H., Guilloux, J.-P., Martinowich, K., Lewis, D. A., & Sibille, E. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12020248 · Cited by 273 · 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
Self-citationBillings, A. G., Cronkite, R. C., & Moos, R. H. (1983) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.92.2.119 · Cited by 256 · see citing works
Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects
Nugent, A. C., Ballard, E. D., Gould, T. D., Park, L. T., Moaddel, R., Brutsche, N. E., & Zarate, C. A. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0028-2 · Cited by 250 · see citing works
Self-citationGABA-related transcripts in the dorsolateral prefrontal cortex in mood disorders
Sibille, E., Morris, H. M., Kota, R. S., & Lewis, D. A. (2011) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710001616 · Cited by 217 · see citing works
Glykys, J. C., & Módy, I. (2006) · Journal of Neurophysiology · doi:10.1152/jn.01122.2005 · Cited by 216 · see citing works
Sieghart, W., & Savić, M. M. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014449 · Cited by 211 · see citing works
Widman, A. J., & McMahon, L. L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718883115 · Cited by 204 · see citing works
Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines
Ali, F., Gerhard, D. M., Sweasy, K., Pothula, S., Pittenger, C., Duman, R. S., & Kwan, A. C. (2020) · Nature Communications · doi:10.1038/s41467-019-13809-8 · Cited by 196 · see citing works
Sustained increase in α5GABAA receptor function impairs memory after anesthesia
Zurek, A. A., Yu, J., Wang, D.-S., Haffey, S. C., Bridgwater, E. M., Antonello Penna, S., Lecker, I., Lei, G., Chang, T., Salter, E. W., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci76669 · Cited by 184 · see citing works
Kallarackal, A. J., Kvarta, M. D., Cammarata, E., Jaberi, L., Cai, X., Bailey, A. M., & Thompson, S. M. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2588-13.2013 · Cited by 181 · see citing works
Self-citationPerioperative Neurocognitive Disorder
Eckenhoff, R. G., Maze, M., Xie, Z., Culley, D. J., Goodlin, S. J., Zuo, Z., Wei, H., Whittington, R. A., Terrando, N., Orser, B. A., et al. (2019) · Anesthesiology · doi:10.1097/aln.0000000000002956 · Cited by 180 · see citing works
Atack, J. R., Bayley, P. J., Seabrook, G. R., Wafford, K. A., McKernan, R. M., & Dawson, G. R. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.04.018 · Cited by 175 · 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
Self-citationPrenosil, G., Gasser, E. M. S., Rudolph, U., Keist, R., Fritschy, J., & Vogt, K. E. (2006) · Journal of Neurophysiology · doi:10.1152/jn.01199.2005 · Cited by 169 · see citing works
Self-citationBraudeau, J., Delatour, B., Duchon, A., Pereira, P. L., Dauphinot, L., de Chaumont, F., Olivo‐Marín, J., Dodd, R. H., Hérault, Y., & Potier, M. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881111405366 · Cited by 163 · see citing works
Toward achieving optimal response: understanding and managing antidepressant side effects
Kelly, K. E., Posternak, M. A., & Jonathan, E. A. (2008) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2008.10.4/kkelly · Cited by 153 · see citing works
Rivolta, D., Heidegger, T., Scheller, B., Sauer, A., Schaum, M., Birkner, K., Singer, W., Wibral, M., & Uhlhaas, P. J. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv051 · Cited by 145 · see citing works
Banasr, M., Lepack, A., Fee, C., Duric, V., Maldonado-Aviles, J., DiLeone, R., Sibille, E., Duman, R. S., & Sanacora, G. (2017) · Chronic Stress · doi:10.1177/2470547017720459 · Cited by 135 · see citing works
Molecular 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
Self-citationMalherbe, P., Sigel, E., Baur, R., Persohn, E., Richards, J. G., & Möhler, H. (1990) · FEBS Letters · doi:10.1016/0014-5793(90)80118-3 · Cited by 130 · see citing works
Ali, A. B., & Thomson, A. M. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhm160 · Cited by 129 · 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
Self-citationSchulz, J. M., Knoflach, F., Hernandez, M., & Bischofberger, J. (2018) · Nature Communications · doi:10.1038/s41467-018-06004-8 · Cited by 115 · see citing works
Sustained Effects of Rapidly Acting Antidepressants Require BDNF-Dependent MeCP2 Phosphorylation
Kim, J.-W., Autry, A. E., Na, E. S., Adachi, M., Björkholm, C., Kavalali, E. T., & Monteggia, L. M. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00868-8 · Cited by 113 · see citing works
Zanos, P., Nelson, M. E., Highland, J. N., Krimmel, S. R., Georgiou, P., Gould, T. D., & Thompson, S. M. (2017) · eNeuro · doi:10.1523/eneuro.0285-16.2017 · Cited by 106 · see citing works
Self-citationNMDAR antagonist action in thalamus imposes delta oscillations on the hippocampus
Zhang, Y., Yoshida, T., Katz, D. B., & Lisman, J. E. (2012) · Journal of Neurophysiology · doi:10.1152/jn.00072.2012 · Cited by 104 · see citing works
The Association between Anhedonia, Suicidal Ideation, and Suicide Attempts in a Large Student Sample
Winer, E. S., Drapeau, C. W., Veilleux, J. C., & Nadorff, M. R. (2015) · Archives of Suicide Research · doi:10.1080/13811118.2015.1025119 · Cited by 86 · see citing works
Davenport, C. M., Rajappa, R., Katchan, L., Taylor, C. R., Tsai, M., Smith, C. M., de Jong, J. W., Arnold, D. B., Lammel, S., & Krämer, R. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.037 · Cited by 86 · see citing works
Farmer, C. A., Gilbert, J. R., Moaddel, R., George, J., Adeojo, L., Lovett, J., Nugent, A. C., Kadriu, B., Yuan, P., Gould, T. D., et al. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0663-6 · Cited by 85 · see citing works
Self-citationMagnin, E., Francavilla, R., Amalyan, S., Gervais, É., David, L. S., Luo, X., & Topolnik, L. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0567-18.2018 · Cited by 81 · see citing works
Towers, S. K., Gloveli, T., Traub, R. D., Driver, J. E., Engel, D., Fradley, R. L., Rosahl, T. W., Maubach, K. A., Buhl, E., & Whittington, M. A. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.071191 · Cited by 76 · see citing works
Maramai, S., Benchekroun, M., Ward, S. E., & Atack, J. R. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01312 · Cited by 75 · see citing works
Atack, J. R., Maubach, K. A., Wafford, K. A., O'Connor, D. V., Rodrigues, A. D., Evans, D. C., Tattersall, F. D., Chambers, M. S., MacLeod, A. M., Eng, W., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.157636 · Cited by 72 · see citing works
Piantadosi, S. C., French, B. J., Poe, M. M., Timić, T., Marković, B. D., Pabba, M., Seney, M. L., Oh, H., Orser, B. A., Savić, M. M., et al. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00446 · Cited by 67 · see citing works
Safavynia, S. A., Keating, G. L., Speigel, I. A., Fidler, J. A., Kreuzer, M., Rye, D. B., Jenkins, A., & García, P. S. (2016) · Anesthesiology · doi:10.1097/aln.0000000000001134 · Cited by 53 · see citing works
Can Anhedonia Be Considered a Suicide Risk Factor? A Review of the Literature
Bonanni, L., Gualtieri, F., Lester, D., Falcone, G., Nardella, A., Fiorillo, A., & Pompili, M. (2019) · Medicina · doi:10.3390/medicina55080458 · Cited by 52 · see citing works
Martín, J. Z. D. S., Donato, C., Peixoto, J., Aguirre, A., Choudhary, V., Stasi, A. M. D., Lourenço, J., Potier, M., & Bacci, A. (2020) · eLife · doi:10.7554/elife.58731 · Cited by 49 · see citing works
Seizures in Drug-Treated Animals
Miczek, K. A., & Weerts, E. M. (1987) · Science · doi:10.1126/science.235.4793.1127a · Cited by 41 · see citing works
Hipp, J. F., Knoflach, F., Comley, R. A., Ballard, T. M., Honer, M., Trube, G., Gasser, R., Prinssen, E. P. M., Wallace, T. L., Rothfuß, A., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-87307-7 · Cited by 39 · see citing works
Duchon, A., Gruart, A., Albac, C., Delatour, B., Martín, J. Z. D. S., Delgado-Garcia, J. M., Hérault, Y., & Potier, M. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14903 · Cited by 33 · see citing works
Rodgers, F. C., Żarnowska, E. D., Laha, K. T., Engin, E., Zeller, A., Keist, R., Rudolph, U., & Pearce, R. A. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0315-15.2015 · Cited by 32 · see citing works
Self-citationCarreno, F. R., Collins, G. T., Frazer, A., & Lodge, D. J. (2017) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx003 · Cited by 31 · see citing works
Xu, N. Z., Ernst, M. C., Treven, M., Cerne, R., Wakulchik, M., Li, X., Jones, T. M., Gleason, S. D., Morrow, D., Schkeryantz, J. M., et al. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4832-9 · Cited by 29 · see citing works
Xiong, Z., Zhang, K., Ishima, T., Ren, Q., Chang, L., Chen, J., & Hashimoto, K. (2018) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2018.10.005 · Cited by 29 · see citing works
Expression of GABAA receptor α5 subunit-like immunoreactivity in human hippocampus
Wainwright, A., SIRINATHSINGHJI, D. J. S., & Oliver, K. R. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00133-9 · Cited by 24 · see citing works
Manzo, M. A., Wang, D.-S., Li, W. W., Pinguelo, A., Popa, M. O., Khodaei, S., Atack, J. R., Ross, R. A., & Orser, B. A. (2020) · British Journal of Anaesthesia · doi:10.1016/j.bja.2020.11.032 · Cited by 16 · see citing works
Mechanisms associated with the antidepressant-like effects of L-655,708
Bugay, V., McCoy, A. M., Lodge, D. J., Brenner, R., Frazer, A., & Carreno, F. R. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0772-2 · Cited by 11 · see citing works
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Zanos, P., Brown, K. A., Georgiou, P., Yuan, P., Zarate, C. A., Thompson, S. M., & Gould, T. D. (2023) · The Journal of Neuroscience · doi:10.1523/jneurosci.1316-22.2022 · Cited by 115 · see citing works
Self-citationPlasticity 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
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- Authors
- Troppoli, T. A., Zanos, P., Georgiou, P., Gould, T. D., Rudolph, U., & Thompson, S. M.
- Affiliations
- University of Maryland, Baltimore (US)
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Thompson, Scott M.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 92
- Issue
- 3
- Pages
- 216-226
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC9198111
- OpenAlex
- W4200080266
- Cited by
- 29
- References
- 69
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 13 · 2022: 3
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Allergan
- National Institutes of Health (R01GM128183-01A1, R01 MH086828, R01MH095905-01A1, R01-MH107615)
- National Alliance for Research on Schizophrenia and Depression (25623)
- U.S. Department of Veterans Affairs (101BX003631, 101BX004062)
- NARSAD
- Roche
- University of Maryland, Baltimore County (15/300,984)
- 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
- negative allosteric modulators, GABAA receptor, alpha5 subunit, benzodiazepine binding site, anhedonia, chronic stress, depression, reward systems, gamma oscillations, flumazenil, ketamine, target engagement
- MeSH terms
- Animals, Benzodiazepines, Female, gamma-Aminobutyric Acid, Humans, Ketamine, Male, Receptors, GABA-A, Sucrose, N-Methylaspartate, Receptors, GABA, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Mice, Anhedonia
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