Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action
Open accessAbstract
We previously reported that the activity of mesolimbic dopamine neurons of the ventral tegmental area (VTA) is a key determinant of behavioral susceptibility vs resilience to chronic social defeat stress. However, this was based solely on ex vivo measurements, and the in vivo firing properties of VTA dopamine neurons in susceptible and resilient mice, as well as the effects of antidepressant treatments, remain completely unknown. Here, we show that chronic (10 d) social defeat stress significantly increased the in vivo spontaneous firing rates and bursting events in susceptible mice but not in the resilient subgroup. Both the firing rates and bursting events were significantly negatively correlated with social avoidance behavior, a key behavioral abnormality induced by chronic social defeat stress. Moreover, the increased firing rates, bursting events, and avoidance behavior in susceptible mice were completely reversed by chronic (2 week), but not acute (single dose), treatments with the antidepressant medication fluoxetine (20 mg/kg). Chronic social defeat stress increased hyperpolarization-activated cation current (I h) in VTA dopamine neurons, an effect that was also normalized by chronic treatment with fluoxetine. As well, local infusion of I h inhibitors ZD7288 (0.1 μg) or DK-AH 269 (0.6 μg) into the VTA exerted antidepressant-like behavioral effects. Together, these data suggest that the firing patterns of mesolimbic dopamine neurons in vivo mediate an individual's responses to chronic stress and antidepressant action.
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The effect of chronic stress on ventral tegmental area dopamine neuron firing is lasting.
“The effect of chronic stress on VTA DA neuron firing is lasting (37, 65, 66), is driven by activity of intrinsic potassium channels (54), and phasic but not tonic optogenetic stimulation of VTA-NAc projecting neurons promotes susceptibility to CSDS (54, 66–68).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [65]
Antagonism of the BDNF receptor TrkB prevents stress susceptibility.
“Rather, BDNF was responsible for stress susceptibility and antagonism of the BDNF receptor TrkB, prevented susceptibility (37, 38, 54, 65, 67, 68).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [65]
BDNF is responsible for stress susceptibility.
“Rather, BDNF was responsible for stress susceptibility and antagonism of the BDNF receptor TrkB, prevented susceptibility (37, 38, 54, 65, 67, 68).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [65]
Ih current is similarly increased in ventral tegmental area neurons of resilient mice.
“Surprisingly, this current is similarly increased in VTA neurons of resilient mice”
From Neurobiology of resilience (2012) · cites this paper as [73]
Hyper-excitability of ventral tegmental area dopamine neurons in susceptible mice is mediated in part by induction of hyperpolarization-activated cation current (Ih), which increases intrinsic excitability.
“the hyper–excitability of VTA dopamine neurons in susceptible mice is mediated in part by induction of hyperpolarization–activated cation current (Ih), which increases the intrinsic excitability of these neurons73”
From Neurobiology of resilience (2012) · cites this paper as [73]
Increased firing of ventral tegmental area dopamine neurons has long been documented in response to rewards and aversive stimuli, and it has been suggested that they increase salience for both types of stimuli.
“increased firing of VTA dopamine neurons has long been documented in response to rewards as well as to aversive stimuli, and it has been suggested that they increase salience for both types of stimuli24, 73–76”
From Neurobiology of resilience (2012) · cites this paper as [73]
Induction of K+ channels functionally occludes the increased Ih current and actively promotes behavioral resilience.
“such induction of K+ channels functionally occludes the increased Ih current and thereby actively promotes behavioral resilience24, 73”
From Neurobiology of resilience (2012) · cites this paper as [73]
Stress-mediated increases in ventral tegmental area dopamine neuron firing are caused by increased Ih currents.
“The stress-mediated increases in VTA dopamine neuron firing are caused by increased Ih currents [29, 35]”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [29]
Chronic physical or psychosocial stressors increase ventral tegmental area dopamine neuron activity to elicit depression-like behavior.
“Chronic physical or psychosocial stressors increase VTA dopamine neuron activity to elicit depression-like behavior.”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [29]
Following chronic social defeat stress, stress-susceptible animals have increased ventral tegmental area dopamine neuron firing that persists for several weeks after stress termination.
“Following CSDS, stress-susceptible animals have increased VTA dopamine neuron firing [13, 23–29] that persists for several weeks after stress termination [28].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [29]
Two weeks of fluoxetine normalizes Ih currents in dopaminergic neurons after chronic social defeat stress.
“Two weeks of fluoxetine normalizes Ih currents in dopaminergic neurons after CSDS [29]”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [29]
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Cites
Nestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00653-0 · Cited by 3,217 · see citing works
Self-citationKrishnan, V., Han, M.-H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., LaPlant, Q., Graham, A., Lutter, M., Lagace, D. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.09.018 · Cited by 2,307 · cited 8× · see citing works
“…role in social defeat-induced behavioral abnormalities (Berton et al., 2006), and we inferred that the activity of VTA DA neurons, measured in brain slices ex vivo, is a key determinant of behavioral susceptibility vs resilience to social defeat (Krishnan et al., 2007; Feder et al., 2009).”
BackgroundMethodResultInfluentialSelf-citationEssential role of BDNF in the mesolimbic dopamine pathway in social defeat stress
Berton, O., McClung, C. A., DiLeone, R. J., Krishnan, V., Renthal, W., Russo, S. J., Graham, D., Tsankova, N. M., Bolanos, C. A., Rios, M., et al. (2006) · Science · doi:10.1126/science.1120972 · Cited by 2,129 · see citing works
Self-citationThe mesolimbic dopamine reward circuit in depression
Nestler, E. J., & Carlezon, W. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.018 · Cited by 2,059 · see citing works
Self-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
Self-citationPsychobiology and molecular genetics of resilience
Feder, A., Nestler, E. J., & Charney, D. S. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2649 · Cited by 1,272 · see citing works
Self-citationDrugs of Abuse and Stress Trigger a Common Synaptic Adaptation in Dopamine Neurons
Saal, D., Dong, Y., Bonci, A., & Malenka, R. C. (2003) · Neuron · doi:10.1016/s0896-6273(03)00021-7 · Cited by 1,147 · 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
Mania-like behavior induced by disruption of <i>CLOCK</i>
Roybal, K., Theobold, D., Graham, A., DiNieri, J. A., Russo, S. J., Krishnan, V., Chakravarty, S., Peevey, J., Oehrlein, N., Birnbaum, S., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609625104 · Cited by 803 · see citing works
Self-citationSartorius, A., Kiening, K. L., Kirsch, P., von Gall, C. C., Haberkorn, U., Unterberg, A. W., Henn, F. A., & Meyer-Lindenberg, A. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.027 · Cited by 611 · see citing works
Regulation of dopaminergic transmission and cocaine reward by the <i>Clock</i> gene
McClung, C. A., Sidiropoulou, K., Vitaterna, M., Takahashi, J. S., White, F. J., Cooper, D. C., & Nestler, E. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503584102 · Cited by 493 · see citing works
Self-citationChristoph, G., Leonzio, R., & Wilcox, K. (1986) · The Journal of Neuroscience · doi:10.1523/jneurosci.06-03-00613.1986 · Cited by 418 · see citing works
Neuhoff, H., Neu, A. D., Liss, B., & Roeper, J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-04-01290.2002 · Cited by 400 · see citing works
Ji, H., & Shepard, P. D. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0958-07.2007 · Cited by 388 · see citing works
Hierarchical Control of Dopamine Neuron-Firing Patterns by Nicotinic Receptors
Mameli-Engvall, M., Evrard, A., Pons, S., Maskos, U., Svensson, T. H., Changeux, J.-P., & Faure, P. (2006) · Neuron · doi:10.1016/j.neuron.2006.05.007 · Cited by 296 · see citing works
Wanat, M. J., Hopf, F. W., Stuber, G. D., Phillips, P. E. M., & Bonci, A. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.150078 · Cited by 256 · see citing works
Marinelli, M., & White, F. J. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-23-08876.2000 · Cited by 254 · see citing works
Afferent modulation of dopamine neuron firing patterns
Kitai, S. T., Shepard, P. D., Callaway, J. C., & Scroggs, R. S. (1999) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)00040-9 · Cited by 234 · see citing works
On the Slowness of Action of Tricyclic Antidepressant Drugs
Oswald, I., Březinová, V., & Dunleavy, D. L. F. (1972) · The British Journal of Psychiatry · doi:10.1192/bjp.120.559.673 · Cited by 227 · see citing works
Assessing the role of Ih channels in synaptic transmission and mossy fiber LTP
Chevaleyre, V., & Castillo, P. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.142213199 · Cited by 198 · see citing works
Restraint increases dopaminergic burst firing in awake rats
Anstrom, K. K., & Woodward, D. J. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300730 · Cited by 181 · see citing works
Dynamics of the dopaminergic system as a key component to the understanding of depression
Yadid, G., & Friedman, A. (2008) · Progress in brain research · doi:10.1016/s0079-6123(08)00913-8 · Cited by 160 · see citing works
Self-citationIncreased Intracranial Self-Stimulation in Rats After Long-Term Administration of Desipramine
Fibiger, H. C., & Phillips, A. G. (1981) · Science · doi:10.1126/science.7197394 · Cited by 154 · see citing works
Friedman, A., Friedman, Y., Dremencov, E., & Yadid, G. (2008) · Journal of Molecular Neuroscience · doi:10.1007/s12031-007-9016-8 · Cited by 63 · see citing works
Self-citationArencibia‐Albite, F., Paladini, C. A., Williams, J., & Jiménez‐Rivera, C. A. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.08.009 · Cited by 57 · see citing works
In vivo contribution of h‐channels in the septal pacemaker to theta rhythm generation
Kocsis, B., & Li, S. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03678.x · Cited by 55 · see citing works
Inyushin, M. Y., Arencibia‐Albite, F., Vázquez‐Torres, R., Vélez-Hernández, M. E., & Jiménez‐Rivera, C. A. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.01.052 · Cited by 43 · see citing works
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Sorted by citations
The brain reward circuitry in mood disorders
Russo, S. J., & Nestler, E. J. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3381 · Cited by 1,870 · see citing works
Self-citationRusso, S. J., Murrough, J. W., Han, M.-H., Charney, D. S., & Nestler, E. J. (2012) · Nature Neuroscience · doi:10.1038/nn.3234 · Cited by 1,206 · see citing works
Self-citationRapid regulation of depression-related behaviours by control of midbrain dopamine neurons
Chaudhury, D., Walsh, J. J., Friedman, A. K., Juarez, B., Ku, S. M., Koo, J. W., Ferguson, D., Tsai, H.-C., Pomeranz, L., Christoffel, D. J., et al. (2013) · Nature · doi:10.1038/nature11713 · Cited by 1,156 · see citing works
Self-citationDopamine 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
Reward and aversion in a heterogeneous midbrain dopamine system
Lammel, S., Lim, B. K., & Malenka, R. C. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.03.019 · Cited by 804 · 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
Self-citationEnhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience
Friedman, A. K., Walsh, J. J., Juarez, B., Ku, S. M., Chaudhury, D., Wang, J., Li, X., Dietz, D. M., Pan, N., Vialou, V. F., et al. (2014) · Science · doi:10.1126/science.1249240 · Cited by 484 · see citing works
Self-citationNeural Mechanisms of Stress Resilience and Vulnerability
Franklin, T. B., Saab, B. J., & Mansuy, I. M. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.016 · Cited by 500 · see citing works
Neurobiology of Resilience: Interface Between Mind and Body
Cathomas, F., Murrough, J. W., Nestler, E. J., Han, M.-H., & Russo, S. J. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.04.011 · Cited by 296 · see citing works
“It is known that RSDS increases the excitatory Ih current in VTA DA neurons of susceptible mice, and induces even greater increases in Ih in these neurons of resilient mice (51) (53) (54).”
BackgroundSelf-citationAn 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
Ventral tegmental area dopamine revisited: effects of acute and repeated stress
Holly, E. N., & Miczek, K. A. (2016) · Psychopharmacology · doi:10.1007/s00213-015-4151-3 · Cited by 265 · see citing works
Distinct Ventral Pallidal Neural Populations Mediate Separate Symptoms of Depression
Knowland, D., Lilascharoen, V., Pacia, C. P., Shin, S., Wang, E. H.-J., & Lim, B. K. (2017) · Cell · doi:10.1016/j.cell.2017.06.015 · Cited by 273 · see citing works
Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression
Francis, T. C., & Lobo, M. K. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.09.007 · Cited by 230 · see citing works
The molecular and cellular mechanisms of depression: a focus on reward circuitry
Fox, M. E., & Lobo, M. K. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0415-3 · Cited by 232 · see citing works
Defeat stress in rodents: from behavior to molecules
Hammels, C., Pishva, E., De Vry, J., van den Hove, D. L. A., Prickaerts, J., van Winkel, R., Selten, J.-P., Lesch, K.-P., Daskalakis, N. P., Steinbusch, H. W. M., et al. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.10.006 · Cited by 230 · see citing works
Wook Koo, J., Labonté, B., Engmann, O., Calipari, E. S., Juarez, B., Lorsch, Z., Walsh, J. J., Friedman, A. K., Yorgason, J. T., Han, M.-H., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.12.009 · Cited by 231 · see citing works
Self-citationFear-enhancing effects of septal oxytocin receptors
Guzmán, Y. F., Tronson, N. C., Jovasevic, V., Sato, K., Guedea, A. L., Mizukami, H., Nishimori, K., & Radulovic, J. (2013) · Nature Neuroscience · doi:10.1038/nn.3465 · Cited by 215 · see citing works
Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway
Walsh, J. J., Friedman, A. K., Sun, H., Heller, E. A., Ku, S. M., Juarez, B., Burnham, V. L., Mazei-Robison, M. S., Ferguson, D., Golden, S. A., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3591 · Cited by 210 · see citing works
Self-citationChronic stress triggers social aversion via glucocorticoid receptor in dopaminoceptive neurons
Barik, J., Marti, F., Morel, C., Fernandez, S. P., Lanteri, C., Godeheu, G., Tassin, J.-P., Mombereau, C., Faure, P., & Tronche, F. (2013) · Science · doi:10.1126/science.1226767 · Cited by 214 · see citing works
BDNF is a negative modulator of morphine action
Koo, J. W., Mazei-Robison, M. S., Chaudhury, D., Juarez, B., LaPlant, Q., Ferguson, D., Feng, J., Sun, H., Scobie, K. N., Damez-Werno, D., et al. (2012) · Science · doi:10.1126/science.1222265 · Cited by 189 · see citing works
Self-citationResilience to chronic stress is mediated by noradrenergic regulation of dopamine neurons
Isingrini, E., Perret, L., Rainer, Q., Amilhon, B., Guma, E., Tanti, A., Martin, G., Robinson, J., Moquin, L., Marti, F., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4245 · Cited by 177 · see citing works
Peripheral and central mechanisms of stress resilience
Pfau, M. L., & Russo, S. J. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.09.004 · Cited by 170 · see citing works
Circadian rhythms and mood regulation: insights from pre-clinical models
McClung, C. A. (2011) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2011.07.008 · Cited by 169 · see citing works
KCNQ channel openers reverse depressive symptoms via an active resilience mechanism
Friedman, A. K., Juarez, B., Ku, S. M., Zhang, H., Calizo, R. C., Walsh, J. J., Chaudhury, D., Zhang, S., Hawkins, A., Dietz, D. M., et al. (2016) · Nature Communications · doi:10.1038/ncomms11671 · Cited by 172 · 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
“Our findings complement previous work showing that CSDS decreases preference for natural rewards (12,13,15) and indicate that ICSS is a sensitive, reliable, and quantifiable method for detecting anhedonic effects of CSDS over time in mice.”
BackgroundResultInfluentialSelf-citationUpdate in the methodology of the chronic stress paradigm: internal control matters
Strekalova, T., Couch, Y., Kholod, N., Boyks, M., Malin, D., Leprince, P., & Steinbusch, H. M. (2011) · Behavioral and Brain Functions · doi:10.1186/1744-9081-7-9 · Cited by 163 · see citing works
Miczek, K. A., Nikulina, E. M., Shimamoto, A., & Covington, H. E. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0637-11.2011 · Cited by 162 · see citing works
Self-citationNucleus Accumbens Modulation in Reward and Aversion
Klawonn, A. M., & Malenka, R. C. (2018) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2018.83.037457 · Cited by 163 · see citing works
Stress responses and the mesolimbic dopamine system: Social contexts and sex differences
Trainor, B. C. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.08.013 · Cited by 138 · see citing works
Sartiani, L., Mannaioni, G., Masi, A., Novella Romanelli, M., & Cerbai, E. (2017) · Pharmacological Reviews · doi:10.1124/pr.117.014035 · Cited by 143 · see citing works
Lüscher, B., & Möhler, H. (2019) · F1000Research · doi:10.12688/f1000research.18758.1 · Cited by 105 · see citing works
Role of Mesolimbic Brain-Derived Neurotrophic Factor in Depression
Koo, J. W., Chaudhury, D., Han, M.-H., & Nestler, E. J. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.020 · Cited by 112 · see citing works
Self-citationAnhedonia in depression symptomatology: appetite dysregulation and defective brain reward processing
Coccurello, R. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112041 · Cited by 106 · see citing works
Kronman, H., Torres-Berrío, A., Sidoli, S., Issler, O., Godino, A., Ramakrishnan, A., Mews, P., Lardner, C. K., Parise, E. M., Walker, D. M., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00814-8 · Cited by 108 · see citing works
Self-citationHCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress
Zhong, P., Vickstrom, C. R., Liu, X., Hu, Y., Yu, L., Yu, H.-G., & Liu, Q.-S. (2018) · eLife · doi:10.7554/elife.32420 · Cited by 99 · see citing works
“VTA dopamine neuron AP firing is altered in chronic stress models of depression (Cao et al., 2010; Chang and Grace, 2014; Moreines et al., 2017; Tye et al., 2013), and modulating this firing can reverse or enhance the development and/or expression of depression-like behavior (Chaudhury et al.,…”
BackgroundMethodInfluentialProgress in understanding mood disorders: optogenetic dissection of neural circuits
Lammel, S., Tye, K. M., & Warden, M. R. (2014) · Genes, Brain and Behavior · doi:10.1111/gbb.12049 · Cited by 98 · see citing works
Zhang, H., Chaudhury, D., Nectow, A. R., Friedman, A. K., Zhang, S., Juarez, B., Liu, H., Pfau, M. L., Aleyasin, H., Jiang, C., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.08.020 · Cited by 88 · see citing works
Self-citationRichey, J. A., Brewer, J. A., Sullivan-Toole, H., Strege, M. V., Kim-Spoon, J., White, S. W., & Ollendick, T. H. (2019) · Clinical Psychology Review · doi:10.1016/j.cpr.2019.101756 · Cited by 79 · see citing works
Fernandez, S. P., Broussot, L., Marti, F., Contesse, T., Mouska, X., Soiza-Reilly, M., Marie, H., Faure, P., & Barik, J. (2018) · Nature Communications · doi:10.1038/s41467-018-06809-7 · Cited by 75 · see citing works
HCN Channels Modulators: The Need for Selectivity
Novella Romanelli, M., Sartiani, L., Masi, A., Mannaioni, G., Manetti, D., Mugelli, A., & Cerbai, E. (2016) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026616999160315130832 · Cited by 73 · see citing works
The Formation and Function of the VTA Dopamine System
Hou, G., Hao, M., Duan, J., & Han, M.-H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073875 · Cited by 65 · see citing works
Self-citationSex differences in effects of dopamine D1 receptors on social withdrawal
Campi, K. L., Greenberg, G. D., Kapoor, A., Ziegler, T. E., & Trainor, B. C. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.09.026 · Cited by 55 · see citing works
HCN Channel Targets for Novel Antidepressant Treatment
Ku, S. M., & Han, M.-H. (2017) · Neurotherapeutics · doi:10.1007/s13311-017-0538-7 · Cited by 54 · see citing works
Self-citationLi, L., Sun, H., Ding, J., Niu, C., Su, M., Zhang, L., Li, Y., Wang, C., Gamper, N., Du, X., et al. (2017) · British Journal of Pharmacology · doi:10.1111/bph.14026 · Cited by 51 · see citing works
Rappeneau, V., & Castillo Díaz, F. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105675 · Cited by 51 · see citing works
“Additionally, research has shown increased firing rates of VTA-DA neurons during aggressive confrontations in male Sprague-Dawley rats (Anstrom et al., 2009) and in C57BL/6 male mice susceptible to SDS (i.e., showing social avoidance) (Cao et al., 2010).”
BackgroundGreenberg, G. D., Steinman, M. Q., Doig, I. E., Hao, R., & Trainor, B. C. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.13099 · Cited by 49 · see citing works
Kim, J., Lei, Y., Lu, X.-Y., & Kim, C. S. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01682-9 · Cited by 33 · see citing works
Fernández Macedo, G. V., Cladouchos, M. L., Sifonios, L., Cassanelli, P. M., & Wikinski, S. (2013) · Psychopharmacology · doi:10.1007/s00213-012-2859-x · Cited by 27 · see citing works
Adolescent but not adult-born neurons are critical for susceptibility to chronic social defeat
Kirshenbaum, G. S., Lieberman, S. R., Briner, T. J., Leonardo, E. D., & Dranovsky, A. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00289 · Cited by 23 · see citing works
Feng, M., Crowley, N. A., Patel, A., Guo, Y., Bugni, S. E., & Luscher, B. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.03.003 · Cited by 20 · see citing works
Grupe, M., Bentzen, B. H., Benned-Jensen, T., Nielsen, V., Frederiksen, K., Jensen, H. S., Jacobsen, A.-M., Skibsbye, L., Sams, A. G., Grunnet, M., et al. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173440 · Cited by 19 · 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
Self-citationLyman, K. A., Han, Y., Zhou, C., Renteria, I., Besing, G.-L., Kurz, J. E., & Chetkovich, D. M. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abl4580 · Cited by 17 · see citing works
Zayed, A., Baranowski, C., Compagnion, A.-C., Vernochet, C., Karaki, S., Cuttoli, R. D.-D., Saint-Jour, E., Bhattacharya, S., Marti, F., Vanhoutte, P., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29380-8 · Cited by 17 · see citing works
Antidepressant-like activity of a brain penetrant HCN channel inhibitor in mice
Pinares-Garcia, P., Spyrou, J., McKenzie, C. E., Forster, I. C., Soh, M. S., Mohamed Syazwan, E., Atif, M., & Reid, C. A. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1159527 · Cited by 15 · see citing works
Teichman, E. M., Hu, J., Lin, H.-Y., Fisher-Foye, R. L., Blando, A., Hu, X., Kaniskan, H. Ü., Montgomery, S. E., Cai, M., Parise, L. F., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-02972-8 · Cited by 5 · see citing works
Self-citation
- Authors
- Cao, J.-L., Covington, H. E., Friedman, A. K., Wilkinson, M. B., Walsh, J. J., Cooper, D. C., Nestler, E. J., & Han, M.-H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Han, Ming-Hu
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-12-08
- Volume
- 30
- Issue
- 49
- Pages
- 16453-16458
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3061337
- OpenAlex
- W2014095642
- Cited by
- 402
- References
- 27
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 24 · 2023: 28 · 2022: 33 · 2021: 35 · 2020: 15 · 2019: 42 · 2018: 28 · 2017: 30 · 2016: 22 · 2015: 23 · 2014: 25 · 2013: 19 · 2012: 24
- FWCI
- 7.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute of Mental Health (R01MH092306, R01MH051399)
- National Institute on Drug Abuse (K01DA017750)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- mesolimbic dopamine neurons, ventral tegmental area, chronic social defeat stress, social avoidance, resilience, antidepressant action, fluoxetine, spontaneous firing rate, burst firing, hyperpolarization-activated current, ZD7288, brain reward circuits
- MeSH terms
- Action Potentials, Analysis of Variance, Animals, Benzazepines, Brain, Cardiotonic Agents, Chronic Disease, Disease Models, Animal, Disease Susceptibility, Dopamine, Electric Stimulation, Fluoxetine, Male, Mice, Inbred C57BL, Neural Pathways, Neurons, Pyrimidines, Reward, Stress, Psychological, Ventral Tegmental Area, Patch-Clamp Techniques, Antidepressive Agents, Second-Generation, Mice
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