Activation of GABAergic Neurons in the Interpeduncular Nucleus Triggers Physical Nicotine Withdrawal Symptoms
Open accessAbstract
Background Chronic exposure to nicotine elicits physical dependence in smokers, yet the mechanism and neuroanatomical bases for withdrawal symptoms are unclear. As in humans, rodents undergo physical withdrawal symptoms after cessation from chronic nicotine characterized by increased scratching, head nods, and body shakes.Results Here we show that induction of physical nicotine withdrawal symptoms activates GABAergic neurons within the interpeduncular nucleus (IPN). Optical activation of IPN GABAergic neurons via light stimulation of channelrhodopsin elicited physical withdrawal symptoms in both nicotine-naive and chronic-nicotine-exposed mice. Dampening excitability of GABAergic neurons during nicotine withdrawal through IPN-selective infusion of an NMDA receptor antagonist or through blockade of IPN neurotransmission from the medial habenula reduced IPN neuronal activation and alleviated withdrawal symptoms. During chronic nicotine exposure, nicotinic acetylcholine receptors containing the β4 subunit were upregulated in somatostatin interneurons clustered in the dorsal region of the IPN. Blockade of these receptors induced withdrawal signs more dramatically in nicotine-dependent compared to nicotine-naive mice and activated nonsomatostatin neurons in the IPN.Conclusions Together, our data indicate that therapeutic strategies to reduce IPN GABAergic neuron excitability during nicotine withdrawal, for example, by activating nicotinic receptors on somatostatin interneurons, may be beneficial for alleviating withdrawal symptoms and facilitating smoking cessation.
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Lidocaine infusion into the MHb to inhibit signaling significantly blocks somatic symptoms from both mecamylamine-precipitated and spontaneous nicotine withdrawal.
“Furthermore, lidocaine infusion into the MHb to inhibit signaling significantly blocks the manifestations of somatic symptoms resulting from both mecamylamine-precipitated and spontaneous induction of nicotine withdrawal (Zhao-Shea et al. 2013).”
From Nicotine Withdrawal (2015) · cites this paper as Zhao-Shea et al. 2013
The Results section (“Glutamate release from MHb-IPN afferents is necessary for somatic nicotine withdrawal signs”; page unavailable) reports that lidocaine infusion into the MHb significantly blocked somatic signs during spontaneous withdrawal. For mecamylamine-precipitated withdrawal, it reports reduced IPN neuronal activation measured by c-Fos, not a significant reduction in somatic symptoms. (LLM, conf=0.91)
Experimental — accuracy not yet measuredThrough the MHb-IPN projection, the MHb releases acetylcholine, substance P, and glutamate onto the IPN.
“Through this projection, the MHb releases acetylcholine (ACh), substance P (SP), and glutamate onto the IPN (Zhao-Shea et al. 2013).”
From Nicotine Withdrawal (2015) · cites this paper as Zhao-Shea et al. 2013
The Results section, “Glutamate release from MHb-IPN afferents is necessary for somatic nicotine withdrawal signs,” says that cholinergic afferents from the MHb also release glutamate into the IPN. The Discussion likewise describes cholinergic input and glutamate release, but our copy does not say that this projection releases substance P. (LLM, conf=0.86)
Experimental — accuracy not yet measuredInfusion of an α3β4* nAChR-selective antagonist into the IPN elicits somatic withdrawal signs in nicotine-naïve mice and more total symptoms in chronically nicotine-treated mice.
“Additionally, infusion of an α3β4* nAChR-selective antagonist into the IPN elicited somatic withdrawal signs in nicotine-naïve mice and an even greater number of total symptoms in mice chronically treated with nicotine (Zhao-Shea et al. 2013).”
From Nicotine Withdrawal (2015) · cites this paper as Zhao-Shea et al. 2013
After precipitated nicotine withdrawal in wild-type mice, there are elevated markers of neuronal activation in GABAergic IPN cells.
“Following precipitated nicotine withdrawal in WT mice, there are elevated markers of neuronal activation in GABAergic IPN cells (Zhao-Shea et al. 2013).”
From Nicotine Withdrawal (2015) · cites this paper as Zhao-Shea et al. 2013
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Cites
Guide for the Care and Use of Laboratory Animals: Eighth Edition
(2011) · doi:10.17226/12910 · Cited by 16,199 · see citing works
A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex
Taniguchi, H., He, M., Wu, P., Kim, S., Paik, R., Sugino, K., Kvitsani, D., Fu, Y., Lu, J., Lin, Y., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.026 · Cited by 1,828 · see citing works
The development and application of optogenetics
Fenno, L., Yizhar, O., & Deisseroth, K. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113817 · Cited by 1,822 · see citing works
Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning
Tsai, H.-C., Zhang, F., Adamantidis, A., Stuber, G. D., Bonci, A., de Lecea, L., & Deisseroth, K. (2009) · Science · doi:10.1126/science.1168878 · Cited by 1,266 · 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
Cole, A. J., Saffen, D. W., Baraban, J. M., & Worley, P. F. (1989) · Nature · doi:10.1038/340474a0 · Cited by 1,010 · see citing works
The habenula: from stress evasion to value-based decision-making
Hikosaka, O. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2866 · Cited by 955 · see citing works
Habenular α5 nicotinic receptor subunit signalling controls nicotine intake
Fowler, C. D., Lu, Q., Johnson, P. M., Marks, M. J., & Kenny, P. J. (2011) · Nature · doi:10.1038/nature09797 · Cited by 663 · see citing works
GABA Neurons of the VTA Drive Conditioned Place Aversion
Tan, K. R., Yvon, C., Turiault, M., Mirzabekov, J. J., Doehner, J., Labouèbe, G., Deisseroth, K. A., Tye, K. M., & Lüscher, C. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.015 · Cited by 635 · see citing works
Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex
Covington, H. E., Lobo, M. K., Maze, I., Vialou, V., Hyman, J. M., Zaman, S., LaPlant, Q., Mouzon, E., Ghose, S., Tamminga, C. A., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1731-10.2010 · Cited by 621 · see citing works
Neurobiology of Nicotine Addiction: Implications for Smoking Cessation Treatment
Benowitz, N. L. (2008) · The American Journal of Medicine · doi:10.1016/j.amjmed.2008.01.015 · Cited by 385 · see citing works
Ren, J., Qin, C., Hu, F., Tan, J., Qiu, L., Zhao, S., Feng, G., & Luo, M. (2011) · Neuron · doi:10.1016/j.neuron.2010.12.038 · Cited by 315 · see citing works
Neurobiology of the nicotine withdrawal syndrome
Kenny, P. J., & Markou, A. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00651-7 · Cited by 310 · see citing works
Salas, R., Sturm, R., Boulter, J., & De Biasi, M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4934-08.2009 · Cited by 310 · see citing works
Frahm, S., Ślimak, M. A., Ferrarese, L., Santos-Torres, J., Antolin-Fontes, B., Auer, S., Filkin, S., Pons, S., Fontaine, J.-F., Tsetlin, V., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.013 · Cited by 283 · see citing works
Salas, R., Pieri, F., & De Biasi, M. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1939-04.2004 · Cited by 226 · see citing works
Characterization of spontaneous and precipitated nicotine withdrawal in the mouse
Damaj, M. I., Kao, W., & Martin, B. R. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.054908 · Cited by 222 · see citing works
Grady, S. R., Moretti, M., Zoli, M., Marks, M. J., Zanardi, A., Pucci, L., Clementi, F., & Gotti, C. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5121-08.2009 · Cited by 222 · see citing works
Watkins, S. S., Stinus, L., Koob, G. F., & Markou, A. (2000) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35389-3 · Cited by 214 · see citing works
Jackson, K. J., Martin, B. R., Changeux, J. P., & Damaj, M. I. (2008) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.132977 · Cited by 208 · see citing works
Molecular Mechanisms Underlying Behaviors Related to Nicotine AddictionPreprint
Picciotto, M. R., & Kenny, P. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012112 · Cited by 178 · see citing works
Somatostatin Inhibits Excitatory Transmission at Rat Hippocampal Synapses via Presynaptic Receptors
Boehm, S., & Betz, H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-11-04066.1997 · Cited by 163 · see citing works
Contestabile, R. A., & Flumerfelt, B. A. (1981) · The Journal of Comparative Neurology · doi:10.1002/cne.901960206 · Cited by 156 · see citing works
Hendrickson, L. M., Zhao-Shea, R., Pang, X.-Y., Gardner, P. D., & Tapper, A. R. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2601-10.2010 · Cited by 101 · see citing works
Self-citationNicotine physical dependence and tolerance in the mouse following chronic oral administration
Grabus, S. D., Martin, B. R., Batman, A. M., Tyndale, R. F., Sellers, E. M., & Damaj, M. I. (2004) · Psychopharmacology · doi:10.1007/s00213-004-2007-3 · Cited by 97 · see citing works
Plaza‐Zabala, A., Flores, Á., Maldonado, R. J., & Berrendero, F. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.06.025 · Cited by 81 · see citing works
Salas, R., Main, A., Gangitano, D., & De Biasi, M. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.08.017 · Cited by 76 · see citing works
Interpeduncular nucleus organization in the rat: Cytoarchitecture and histochemical analysis
Hemmendinger, L. M., & Moore, R. Y. (1984) · Brain Research Bulletin · doi:10.1016/0361-9230(84)90018-2 · Cited by 70 · see citing works
A study of afferent projections to the rat interpeduncular nucleus
Hamill, G. S., & Jacobowitz, D. M. (1984) · Brain Research Bulletin · doi:10.1016/0361-9230(84)90035-2 · Cited by 68 · see citing works
Zaveri, N. T., Jiang, F., Olsen, C. M., Polgar, W. E., & Toll, L. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm1006148 · Cited by 53 · see citing works
Stoker, A. K., Olivier, B., & Markou, A. (2012) · Behavior Genetics · doi:10.1007/s10519-011-9511-0 · Cited by 40 · see citing works
Cholinergic and non-cholinergic forebrain projections to the interpenduncular nucleus
Albanese, A., Castagna, M., & Altavista, M. C. (1985) · Brain Research · doi:10.1016/0006-8993(85)90545-1 · Cited by 38 · see citing works
Kawaja, M. D., Flumerfelt, B. A., & Hrycyshyn, A. W. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90166-8 · Cited by 12 · see citing works
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Le Foll, B., Piper, M. E., Fowler, C. D., Tonstad, S., Bierut, L., Lu, L., Jha, P., & Hall, W. D. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00346-w · Cited by 316 · see citing works
McLaughlin, I., Dani, J. A., & Biasi, M. D. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14008 · Cited by 223 · see citing works
Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction
Wittenberg, R. E., Wolfman, S. L., Biasi, M. D., & Dani, J. A. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108256 · Cited by 200 · see citing works
McLaughlin, I., Dani, J. A., & De Biasi, M. (2015) · Current Topics in Behavioral Neurosciences · doi:10.1007/978-3-319-13482-6_4 · Cited by 173 · see citing works
“Through this projection, the MHb releases acetylcholine (ACh), substance P (SP), and glutamate onto the IPN (Zhao-Shea et al. 2013).”
BackgroundInfluentialZhao-Shea, R., DeGroot, S. R., Liu, L., Vallaster, M., Pang, X.-Y., Su, Q., Gao, G., Rando, O. J., Martin, G. E., George, O., et al. (2015) · Nature Communications · doi:10.1038/ncomms7770 · Cited by 166 · see citing works
Self-citationThe habenulo-interpeduncular pathway in nicotine aversion and withdrawal
Antolin-Fontes, B., Ables, J. L., Görlich, A., & Ibañez-Tallon, I. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.11.019 · Cited by 154 · see citing works
Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety
Nguyen, C., Mondoloni, S., Le Borgne, T., Centeno, I., Come, M., Jehl, J., Solié, C., Reynolds, L. M., Durand-de Cuttoli, R., Tolu, S., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.06.013 · Cited by 136 · see citing works
Shih, P.-Y., Engle, S. E., Oh, G., Deshpande, P., Puskar, N. L., Lester, H. A., & Drenan, R. M. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0476-14.2014 · Cited by 136 · see citing works
Neurobiological Mechanisms of Nicotine Reward and Aversion
Wills, L. P., Ables, J. L., Braunscheidel, K. M., Caligiuri, S. P. B., Elayouby, K. S., Fillinger, C., Ishikawa, M., Moen, J. K., & Kenny, P. J. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000299 · Cited by 126 · see citing works
Pistillo, F., Clementi, F., Zoli, M., & Gotti, C. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.10.002 · Cited by 113 · see citing works
Anatomical and single-cell transcriptional profiling of the murine habenular complex
Wallace, M. L., Huang, K. W., Hochbaum, D., Hyun, M., Radeljic, G., & Sabatini, B. L. (2020) · eLife · doi:10.7554/elife.51271 · Cited by 113 · see citing works
New mechanisms and perspectives in nicotine withdrawal
Jackson, K. J., Muldoon, P. P., Biasi, M. D., & Damaj, M. I. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.11.009 · Cited by 103 · see citing works
Anxiety and Nicotine Dependence: Emerging Role of the Habenulo-Interpeduncular Axis
Molas, S., DeGroot, S. R., Zhao-Shea, R., & Tapper, A. R. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.11.001 · Cited by 100 · see citing works
Self-citationAn essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence
Frahm, S., Antolin-Fontes, B., Görlich, A., Zander, J.-F., Ahnert-Hilger, G., & Ibañez-Tallon, I. (2015) · eLife · doi:10.7554/elife.11396 · Cited by 98 · see citing works
Mineur, Y. S., Fote, G. M., Blakeman, S., Cahuzac, E. L. M., Newbold, S. A., & Picciotto, M. R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.316 · Cited by 90 · see citing works
Mammalian Susceptibility to a Neonicotinoid Insecticide after Fetal and Early Postnatal Exposure
Burke, A., Niibori, Y., Terayama, H., Ito, M., Pidgeon, C., Arsenault, J., Camarero, P. R., Cummins, C. L., Mateo, R., Sakabe, K., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-35129-5 · Cited by 75 · see citing works
Goldberg, L. R., & Gould, T. J. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14060 · Cited by 88 · see citing works
Quina, L. A., Harris, J. A., Zeng, H., & Turner, E. E. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24221 · Cited by 85 · see citing works
Pang, X.-Y., Liu, L., Ngolab, J., Zhao-Shea, R., McIntosh, J. M., Gardner, P. D., & Tapper, A. R. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.03.039 · Cited by 84 · see citing works
Self-citationNicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum
Wolfman, S. L., Gill, D. F., Bogdanic, F., Long, K., Al-Hasani, R., McCall, J. G., Bruchas, M. R., & McGehee, D. S. (2018) · Nature Communications · doi:10.1038/s41467-018-04654-2 · Cited by 81 · see citing works
Lima, L. B., Bueno, D., Leite, F., Souza, S., Gonçalves, L., Furigo, I. C., Donato, J., & Metzger, M. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24217 · Cited by 80 · see citing works
Understanding the habenula: A major node in circuits regulating emotion and motivation
Ables, J. L., Park, K., & Ibáñez-Tallon, I. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106734 · Cited by 76 · see citing works
Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring
Vallaster, M., Kukreja, S., Bing, X., Ngolab, J., Zhao-Shea, R., Gardner, P. D., Tapper, A. R., & Rando, O. J. (2017) · eLife · doi:10.7554/elife.24771 · Cited by 75 · see citing works
Self-citationA circuit-based mechanism underlying familiarity signaling and the preference for novelty
Molas, S., Zhao-Shea, R., Liu, L., DeGroot, S. R., Gardner, P. D., & Tapper, A. R. (2017) · Nature Neuroscience · doi:10.1038/nn.4607 · Cited by 72 · see citing works
Self-citationDeGroot, S. R., Zhao-Shea, R., Chung, L., Klenowski, P. M., Sun, F., Molas, S., Gardner, P. D., Li, Y., & Tapper, A. R. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.06.018 · Cited by 71 · see citing works
Self-citationThe Role of the Medial Habenula Cholinergic System in Addiction and Emotion-Associated Behaviors
Lee, H. W., Yang, S. H., Kim, J. Y., & Kim, H. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00100 · Cited by 69 · see citing works
Rodent models for nicotine withdrawal
Chellian, R., Behnood‐Rod, A., Bruijnzeel, D. M., Wilson, R., Pandy, V., & Bruijnzeel, A. W. (2021) · Journal of Psychopharmacology · doi:10.1177/02698811211005629 · Cited by 68 · see citing works
Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
Han, S., Yang, S. H., Kim, J. Y., Mo, S., Yang, E., Song, K. M., Ham, B., Mechawar, N., Turecki, G., Lee, H. W., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01088-6 · Cited by 62 · see citing works
Addiction‐related neuroadaptations following chronic nicotine exposure
Wills, L., & Kenny, P. J. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15356 · Cited by 61 · see citing works
Ables, J. L., Görlich, A., Antolin‐Fontes, B., Wang, C., Lipford, S. M., Riad, M. H., Ren, J., Hu, F., Luo, M., Kenny, P. J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717506114 · Cited by 61 · see citing works
Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates
Jester-Broms, J., Antolin‐Fontes, B., Tingström, A., & Ibáñez-Tallon, I. (2014) · The Journal of Comparative Neurology · doi:10.1002/cne.23664 · Cited by 54 · see citing works
Kawai, H., Bouchekioua, Y., Nishitani, N., Niitani, K., Izumi, S., Morishita, H., Andoh, C., Nagai, Y., Koda, M., Hagiwara, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35346-7 · Cited by 54 · see citing works
Morton, G., Nasirova, N., Sparks, D. W., Brodsky, M., Sivakumaran, S., Lambe, E. K., & Turner, E. E. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0023-18.2018 · Cited by 48 · see citing works
Roman, E., Weininger, J., Lim, B., Roman, M., Barry, D., Tierney, P., O’Hanlon, E., Levins, K., O’Keane, V., & Roddy, D. (2020) · Brain Structure and Function · doi:10.1007/s00429-020-02069-8 · Cited by 44 · see citing works
Chronic Nicotine Exposure Alters the Neurophysiology of Habenulo-Interpeduncular Circuitry
Arvin, M. C., Jin, X.-T., Yan, Y., Wang, Y., Ramsey, M. D., Kim, V. J., Beckley, N. A., Henry, B. A., & Drenan, R. M. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.2816-18.2019 · Cited by 42 · see citing works
A neuronal coping mechanism linking stress-induced anxiety to motivation for reward
Klenowski, P. M., Zhao-Shea, R., Freels, T. G., Molas, S., Zinter, M., M'angale, P. G., Xiao, C., Martínez‐Núñez, L., Thomson, T., & Tapper, A. R. (2023) · Science Advances · doi:10.1126/sciadv.adh9620 · Cited by 33 · see citing works
Self-citationHarrington, L., Viñals, X., Herrera-Solís, A., Flores, Á., Morel, C., Tolu, S., Fauré, P., Maldonado, R. J., Maskos, U., & Robledo, P. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.346 · Cited by 36 · see citing works
Klenowski, P. M., Zhao-Shea, R., Freels, T. G., Molas, S., & Tapper, A. R. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01107-1 · Cited by 36 · see citing works
Self-citationCorrea, V. L., Flores, R. J., Carcoba, L. M., Arreguin, M. C., & O’Dell, L. E. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107714 · Cited by 33 · see citing works
Ngolab, J., Liu, L., Zhao-Shea, R., Gao, G., Gardner, P. D., & Tapper, A. R. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4453-14.2015 · Cited by 32 · see citing works
Self-citationMemantine improves buprenorphine/naloxone treatment for opioid dependent young adults
Gonzalez, G. M., DiGirolamo, G. J., Romero-González, M., Smelson, D. A., Ziedonis, D. M., & Kolodziej, M. E. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.09.020 · Cited by 31 · see citing works
The Interpeduncular-Ventral Hippocampus Pathway Mediates Active Stress Coping and Natural Reward
Sherafat, Y., Bautista, M. R., Fowler, J. P., Chen, E., Ahmed, A., & Fowler, C. D. (2020) · eNeuro · doi:10.1523/eneuro.0191-20.2020 · Cited by 30 · see citing works
Renda, A., & Nashmi, R. (2014) · BMC Neuroscience · doi:10.1186/1471-2202-15-89 · Cited by 31 · see citing works
Sadahiro, M., Demars, M. P., Burman, P., Yevoo, P., Zimmer, A., & Morishita, H. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.1373-19.2020 · Cited by 29 · see citing works
GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals
Bhandari, P., Vandael, D. H. F., Fernández‐Fernández, D., Fritzius, T., Kleindienst, D., Önal, C., Montanaro, J., Gassmann, M., Jónás, P., Kulik, Á., et al. (2021) · eLife · doi:10.7554/elife.68274 · Cited by 28 · see citing works
Bailly, J., Allain, F., Schwartz, E., Tirel, C., Dupuy, C., Petit, F., Diana, M. A., Darcq, E., & Kieffer, B. L. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.09.013 · Cited by 28 · see citing works
Lee, S.-J., Woo, J., Kim, Y. S., & Im, H. (2015) · Scientific Reports · doi:10.1038/srep12909 · Cited by 27 · see citing works
Liu, W., & Li, M. D. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170801103009 · Cited by 27 · see citing works
Icick, R., Forget, B., Cloëz-Tayarani, I., Pons, S., Maskos, U., & Besson, M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108234 · Cited by 26 · see citing works
Differential Nicotinic Modulation of Glutamatergic and GABAergic VTA Microcircuits
Yan, Y., Beckley, N. A., Kim, V. J., & Drenan, R. M. (2019) · eNeuro · doi:10.1523/eneuro.0298-19.2019 · Cited by 24 · see citing works
Souter, E. A., Chen, Y.-C., Zell, V., Lallai, V., Steinkellner, T., Conrad, W. S., Wisden, W., Harris, K. D., Fowler, C. D., & Hnasko, T. S. (2021) · eNeuro · doi:10.1523/eneuro.0481-21.2021 · Cited by 23 · see citing works
Shih, P.-Y., McIntosh, J. M., & Drenan, R. M. (2015) · Molecular Pharmacology · doi:10.1124/mol.115.101444 · Cited by 23 · see citing works
Multidimensional Intersection of Nicotine, Gene Expression, and Behavior
Sherafat, Y., Bautista, M. R., & Fowler, C. D. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.649129 · Cited by 22 · see citing works
Mondoloni, S., Nguyen, C., Vicq, É., Ciscato, M., Jehl, J., Cuttoli, R. D.-D., Torquet, N., Tolu, S., Pons, S., Maskos, U., et al. (2023) · eLife · doi:10.7554/elife.80767 · Cited by 21 · see citing works
Cooper, S. Y., Willis, C. V., Richardson, M. R., Hill, S. P., Wright, S. K., Elmore, M. B., Mitchell, Z. B., Castro, A. K. G., & Henderson, B. J. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.0755-22.2022 · Cited by 21 · see citing works
Nicotine Self-Administration Induces Plastic Changes to Nicotinic Receptors in Medial Habenula
Jin, X., Tucker, B. R., & Drenan, R. M. (2020) · eNeuro · doi:10.1523/eneuro.0197-20.2020 · Cited by 21 · see citing works
Molas, S., Zhao-Shea, R., Freels, T. G., & Tapper, A. R. (2023) · eNeuro · doi:10.1523/eneuro.0282-22.2022 · Cited by 24 · see citing works
Self-citationOptogenetic activation of septal GABAergic afferents entrains neuronal firing in the medial habenula
Choi, K., Lee, Y., Lee, C., Hong, S., Lee, S., Kang, S. J., & Shin, K. S. (2016) · Scientific Reports · doi:10.1038/srep34800 · Cited by 19 · see citing works
KCTD8 and KCTD12 Facilitate Axonal Expression of GABABReceptors in Habenula Cholinergic Neurons
Ren, Y., Liu, Y., Zheng, S., & Luo, M. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.1676-21.2021 · Cited by 18 · see citing works
Xu, X., Li, N., Wen, J., Yang, P., Lu, X., Wang, Z., He, T., Fan, Y., Xu, B., Ge, F., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.1767-22.2022 · Cited by 17 · see citing works
Pérez, P. D., Hall, G., Zubcevic, J. A., & Febo, M. (2017) · Brain Imaging and Behavior · doi:10.1007/s11682-017-9691-1 · Cited by 17 · see citing works
Mathuru, A. S. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.09.030 · Cited by 17 · see citing works
Pisera-Fuster, A., Zwiller, J., & Bernabeu, R. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02260-2 · Cited by 17 · see citing works
Tapia, M. A., Jin, X., Tucker, B. R., Thomas, L. N., Walker, N. B., Kim, V. J., Albertson, S. E., Damuka, N., Krizan, I. M., Edassery, S. L., et al. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109066 · Cited by 15 · see citing works
Upton, M. K., & Lotfipour, S. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.06.015 · Cited by 16 · see citing works
Molecular, Neuronal, and Behavioral Effects of Ethanol and Nicotine Interactions
Klenowski, P. M., & Tapper, A. R. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2017_89 · Cited by 15 · see citing works
Self-citationGene editing vectors for studying nicotinic acetylcholine receptors in cholinergic transmission
Peng, C., Yan, Y., Kim, V. J., Engle, S. E., Berry, J. N., McIntosh, J. M., Neve, R. L., & Drenan, R. M. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13957 · Cited by 13 · see citing works
Neuroscience of nicotine for addiction medicine
D’Souza, M. S. (2015) · Progress in brain research · doi:10.1016/bs.pbr.2015.07.008 · Cited by 13 · see citing works
Integrated miRNA-/mRNA-Seq of the Habenulo-Interpeduncular Circuit During Acute Nicotine Withdrawal
Casserly, A. P., Tsuji, J., Zhao-Shea, R., Smith, C. B., Molas, S., Tapper, A. R., Weng, Z., & Gardner, P. D. (2020) · Scientific Reports · doi:10.1038/s41598-020-57907-w · Cited by 12 · see citing works
Self-citationGlial cells as therapeutic targets for smoking cessation
Kumar, M., Adeluyi, A., Anderson, E. L., & Turner, J. R. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108157 · Cited by 12 · see citing works
miRNAome analysis of the mammalian neuronal nicotinic acetylcholine receptor gene family
Hogan, E. M., Casserly, A. P., Scofield, M. D., Mou, Z., Zhao-Shea, R., Johnson, C. W., Tapper, A. R., & Gardner, P. D. (2014) · RNA · doi:10.1261/rna.034066.112 · Cited by 12 · see citing works
Self-citationNew medications development for smoking cessation
Lengel, D., & Kenny, P. J. (2023) · Addiction Neuroscience · doi:10.1016/j.addicn.2023.100103 · Cited by 12 · see citing works
Carcoba, L. M., Uribe, K. P., Ortegon, S., Mendez, I. A., Biasi, M. D., & O’Dell, L. E. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24826 · Cited by 11 · see citing works
Convergence of signaling pathways underlying habenular formation and axonal outgrowth in zebrafish
Roberson, S., & Halpern, M. E. (2017) · Development · doi:10.1242/dev.147751 · Cited by 11 · see citing works
Pugach, O., Cannon, D. S., Weiss, R. B., Hedeker, D., & Mermelstein, R. J. (2016) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntw197 · Cited by 10 · see citing works
The influence of ovarian hormones on the putative mechanisms that promote female nicotine use
Giner, P., Ortegon, S., Bağdaş, D., & O’Dell, L. E. (2024) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2024.102900 · Cited by 9 · see citing works
Kassner, M., Eaton, J. B., Tang, N., Petit, J. L., Meurice, N., Yin, H. H., & Whiteaker, P. (2022) · SLAS DISCOVERY · doi:10.1016/j.slasd.2021.10.001 · Cited by 9 · see citing works
Functional α7 nicotinic acetylcholine receptors in GABAergic neurons of the interpeduncular nucleus
Jin, X., & Drenan, R. M. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.108987 · Cited by 9 · see citing works
Dumiaty, Y., Underwood, B. M., Phy‐Lim, J., & Chee, M. J. S. (2024) · Neuropeptides · doi:10.1016/j.npep.2024.102427 · Cited by 12 · see citing works
Matos-Ocasio, F., Espinoza, V. E., Correa-Alfonzo, P., Khan, A. M., & O’Dell, L. E. (2021) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2021.108640 · Cited by 9 · see citing works
Neurobiological Considerations for Tobacco Use Disorder
Chawla, M., & Garrison, K. A. (2018) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-018-0168-3 · Cited by 8 · see citing works
Molas, S., Gener, T., Güell‐Bosch, J., Martı́n, M., Ballesteros‐Yáñez, I., Sanchez-Vives, M. V., & Dierssen, M. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0147-1 · Cited by 8 · see citing works
Tsuzuki, A., Yamasaki, M., Konno, K., Miyazaki, T., Takei, N., Tomita, S., Yuzaki, M., & Watanabe, M. (2024) · Scientific Reports · doi:10.1038/s41598-024-65076-3 · Cited by 7 · see citing works
Mu-opioid receptor activation potentiates excitatory transmission at the habenulo-peduncular synapse
Singhal, S. M., Szlaga, A., Chen, Y.-C., Conrad, W. S., & Hnasko, T. S. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115874 · Cited by 7 · see citing works
Anatomical and functional organization of the interpeduncular nucleus in larval zebrafishPreprint
Wu, Y. K., Petrucco, L., & Portugues, R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.09.617353 · Cited by 7 · see citing works
Rakotobé, M., Fjerdingstad, N., Ruiz-Reig, N., Lamonerie, T., & D’Autréaux, F. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106392 · Cited by 5 · see citing works
Jackson, A. B., Toma, W. B., Contreras, K. M., Alkhlaif, Y., & Damaj, M. I. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.05.003 · Cited by 6 · see citing works
Shankar, K., Bonnet-Zahedi, S., & George, O. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06852-5 · Cited by 6 · see citing works
Monical, A., & McGehee, D. S. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.2405-24.2025 · Cited by 7 · see citing works
Chronic nicotine impairs sparse motor learning via striatal fast‐spiking parvalbumin interneurons
Kim, B. S., & Im, H. (2020) · Addiction Biology · doi:10.1111/adb.12956 · Cited by 5 · see citing works
Nishitani, N., Ohmura, Y., Kobayashi, K., Murashita, T., Yoshida, T., & Yoshioka, M. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.05.052 · Cited by 5 · see citing works
Reynaga, D. D., Cano, M., Belluzzi, J. D., & Leslie, F. M. (2023) · Advances in Drug and Alcohol Research · doi:10.3389/adar.2023.11324 · Cited by 5 · see citing works
Ciscato, M., Chouvaeff, M., & Mourot, A. (2025) · European Journal of Neuroscience · doi:10.1111/ejn.70352 · Cited by 4 · see citing works
Avelar, A. J., & George, O. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01185-1 · Cited by 4 · see citing works
Histone Methyltransferase G9a Plays an Essential Role on Nicotine Preference in Zebrafish
Faillace, M. P., Ortiz, J., Rocco, L., & Bernabeu, R. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-03961-8 · Cited by 3 · see citing works
Stinson, H. E., & Ninan, I. (2025) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2025.09.010 · Cited by 3 · see citing works
Harris, A. C. (2021) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2021.173185 · Cited by 3 · see citing works
Kim, B., Kim, H., Woo, J., Lee, H., Kim, T. K., Min, H., Lee, C. J., & Im, H. (2024) · Advanced Science · doi:10.1002/advs.202402274 · Cited by 2 · see citing works
Habenular Synapses and Nicotine
Ables, J. L., Antolin‐Fontes, B., & Ibáñez-Tallon, I. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813035-3.00010-1 · Cited by 2 · see citing works
Khatami, L., Safari, V., & Motamedi, F. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112212 · Cited by 2 · see citing works
- Authors
- Zhao-Shea, R., Liu, L., Pang, X., Gardner, P. D., & Tapper, A. R.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Tapper, Andrew R.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 23
- Issue
- 23
- Pages
- 2327-2335
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC3855889
- OpenAlex
- W1972200439
- Cited by
- 129
- References
- 33
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 9 · 2023: 10 · 2022: 10 · 2021: 16 · 2020: 13 · 2019: 9 · 2018: 7 · 2017: 11 · 2016: 5 · 2015: 16 · 2014: 8 · 2013: 1
- FWCI
- 6.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA017656)
- National Institute on Drug Abuse (R21DA025853)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- nicotine withdrawal, interpeduncular nucleus, GABAergic neurons, somatostatin interneurons, nicotinic acetylcholine receptors, NMDA receptor antagonists, medial habenula, chronic nicotine exposure, smoking cessation, nicotine dependence, neuronal excitability
- MeSH terms
- Animals, Light, Male, Mecamylamine, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Synaptic Transmission, Nicotine, Phototherapy, Receptors, Nicotinic, Rhodopsin, Somatostatin, Substance Withdrawal Syndrome, Receptors, N-Methyl-D-Aspartate, Glutamic Acid, Nicotinic Agonists, Nicotinic Antagonists, Mice, GABAergic Neurons
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