Identifying candidate drivers of alcohol dependence-induced excessive drinking by assembly and interrogation of brain-specific regulatory networks
Open accessAbstract
Background: A systems biology approach based on the assembly and interrogation of gene regulatory networks, or interactomes, was used to study neuroadaptation processes associated with the transition to alcohol dependence at the molecular level. Results: Using a rat model of dependent and non-dependent alcohol self-administration, we reverse engineered a global transcriptional regulatory network during protracted abstinence, a period when relapse rates are highest. We then interrogated the network to identify master regulator genes that mechanistically regulate brain region-specific signatures associated with dependent and non-dependent alcohol self-administration. Among these, the gene coding for the glucocorticoid receptor was independently identified as a master regulator in multiple brain regions, including the medial prefrontal cortex, nucleus accumbens, central nucleus of the amygdala, and ventral tegmental area, consistent with the view that brain reward and stress systems are dysregulated during protracted abstinence. Administration of the glucocorticoid antagonist mifepristone in either the nucleus accumbens or ventral tegmental area selectively decreased dependent, excessive, alcohol self-administration in rats but had no effect on non-dependent, moderate, alcohol self-administration. Conclusions: Our study suggests that assembly and analysis of regulatory networks is an effective strategy for the identification of key regulators of long-term neuroplastic changes within specific brain regions that play a functional role in alcohol dependence. More specifically, our results support a key role for regulatory networks downstream of the glucocorticoid receptor in excessive alcohol drinking during protracted alcohol abstinence.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increased GR activity in the CeA plays a key role in alcohol-dependence associated behaviors.
“increased GR activity in the CeA has been suggested to play a key role in alcohol-dependence associated behaviors (Repunte-Canonigo et al., 2015;Vendruscolo et al., 2015;Vendruscolo et al., 2012).”
From Alcohol dependence and withdrawal increase sensitivity of central amygdalar GABAergic synapses to the glucocorticoid receptor antagonist mifepristone in male rats (2022) · cites this paper as Repunte-Canonigo et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Koob, G. F., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.110 · Cited by 5,340 · see citing works
Self-citationDrug Addiction, Dysregulation of Reward, and Allostasis
Koob, G. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00195-0 · Cited by 2,953 · see citing works
Self-citationMargolin, A. A., Nemenman, I., Basso, K., Wiggins, C., Stolovitzky, G., Favera, R. D., & Califano, A. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-s1-s7 · Cited by 2,420 · see citing works
Self-citationMargolin, A. A., Nemenman, I. M., Basso, K., Wiggins, C. H., Stolovitzky, G. A., Favera, R. D., & Califano, A. (2006) · BMC Bioinformatics · doi:10.7916/d8g15zbp · Cited by 2,260 · see citing works
Self-citationReverse engineering of regulatory networks in human B cells
Basso, K., Margolin, A. A., Stolovitzky, G. A., Klein, U., Dalla‐Favera, R., & Califano, A. (2005) · Nature Genetics · doi:10.1038/ng1532 · Cited by 1,406 · see citing works
Self-citationTRANSFAC: an integrated system for gene expression regulation
Wingender, E. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.316 · Cited by 1,249 · see citing works
The transcriptional network for mesenchymal transformation of brain tumours
Carro, M. S., Lim, W. K., Alvarez, M. J., Bollo, R. J., Zhao, X., Snyder, E. Y., Sulman, E. P., Anne, S. L., Doetsch, F. K., Colman, H., et al. (2009) · Nature · doi:10.1038/nature08712 · Cited by 1,242 · see citing works
Self-citationMutations of multiple genes cause deregulation of NF-kB in diffuse large B-cell lymphoma
Compagno, M., Lim, W., Grunn, A., Nandula, S., Brahmachary, M., Shen, Q., Bertoni, F., Ponzoni, M., Scandurra, M., Califano, A., et al. (2009) · Nature · doi:10.1038/nature07968 · Cited by 1,116 · see citing works
Self-citationMathelier, A., Zhao, X., Zhang, A. W., Parcy, F., Worsley-Hunt, R., Arenillas, D. J., Buchman, S., Chen, C., Chou, A., Ienasescu, H., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt997 · Cited by 983 · see citing works
Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking
Stuber, G. D., Sparta, D. R., Stamatakis, A. M., van Leeuwen, W. A., Hardjoprajitno, J. E., Cho, S., Tye, K. M., Kempadoo, K. A., Zhang, F., Deisseroth, K., et al. (2011) · Nature · doi:10.1038/nature10194 · Cited by 878 · see citing works
Sumazin, P., Yang, X., Chiu, H., Chung, W., Iyer, A. P., Llobet‐Navàs, D., Rajbhandari, P., Bansal, M., Guarnieri, P., Silva, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.09.041 · Cited by 692 · see citing works
Self-citationGlucocorticosteroids: current and future directions
Barnes, P. J. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01199.x · Cited by 534 · see citing works
Limbic and Motor Circuitry Underlying Footshock-Induced Reinstatement of Cocaine-Seeking Behavior
McFarland, K., Davidge, S. B., Lapish, C. C., & Kalivas, P. W. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4177-03.2004 · Cited by 524 · see citing works
REVIEW: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?
Heilig, M., Egli, M., Crabbe, J. C., & Becker, H. C. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2009.00194.x · Cited by 435 · see citing works
Koob, G. F. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_129 · Cited by 428 · see citing works
Self-citationLefèbvre, C., Rajbhandari, P., Alvarez, M. J., Bandaru, P., Lim, W. K., Sato, M., Wang, K., Sumazin, P., Kustagi, M., Bisikirska, B. C., et al. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.31 · Cited by 372 · see citing works
Self-citationKreek, M. J., LaForge, K. S., & Butelman, E. R. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd897 · Cited by 371 · see citing works
Excessive Ethanol Drinking Following a History of Dependence Animal Model of Allostasis
Roberts, A. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00167-0 · Cited by 349 · see citing works
Piazza, P. V., Rougé-Pont, F., Deroche, V, Maccari, S., Simon, H., & Le Moal, M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8716 · Cited by 346 · see citing works
Integrating regulatory motif discovery and genome-wide expression analysis
Conlon, E. M., Liu, X. S., Lieb, J. D., & Liu, J. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0630591100 · Cited by 343 · see citing works
Enhanced Alcohol Self‐Administration after Intermittent Versus Continuous Alcohol Vapor Exposure
O’Dell, L. E., Roberts, A. J., Smith, R. T., & Koob, G. F. (2004) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000145781.11923.4e · Cited by 342 · see citing works
Self-citationRoberto, M., Cruz, M. T., Gilpin, N. W., Sabino, V., Schweitzer, P., Bajo, M., Cottone, P., Madamba, S. G., Stouffer, D. G., Zorrilla, E. P., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.11.007 · Cited by 336 · see citing works
Self-citationCorticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats
Vendruscolo, L. F., Barbier, E., Schlosburg, J. E., Misra, K. K., Whitfield, T. W., Logrip, M. L., Rivier, C., Repunte-Canonigo, V., Zorrilla, E. P., Sanna, P. P., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0069-12.2012 · Cited by 319 · see citing works
Self-citationAytés, À., Mitrofanova, A., Lefèbvre, C., Alvarez, M. J., Castillo-Martín, M., Zheng, T., Eastham, J. A., Gopalan, A., Pienta, K. J., Shen, M. M., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.03.017 · Cited by 319 · see citing works
Self-citationDiana, M., Pistis, M., Carboni, S., Gessa, G. L., & Rossetti, Z. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7966 · Cited by 309 · see citing works
Koob, G. F. (2011) · Current topics in behavioral neurosciences · doi:10.1007/978-3-642-28720-6_129 · Cited by 307 · see citing works
Self-citationDirect reversal of glucocorticoid resistance by AKT inhibition in acute lymphoblastic leukemia
Piovan, E., Yu, J.-Y., Tosello, V., Herranz, D., Ambesi-Impiombato, A., da Silva, A. D., Sanchez-Martin, M., Pérez-García, A., Rigo, I., Castillo, M., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.10.022 · Cited by 259 · see citing works
Self-citationWang, K., Saito, M., Bisikirska, B. C., Alvarez, M. J., Lim, W. K., Rajbhandari, P., Shen, Q. “., Nemenman, I. M., Basso, K., Margolin, A. A., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1563 · Cited by 237 · see citing works
Self-citationPreclinical studies of alcohol binge drinking
Crabbe, J. C., Harris, R. A., & Koob, G. F. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05895.x · Cited by 221 · see citing works
Self-citationRoot, D. H., Mejías-Aponte, C. A., Qi, J., & Morales, M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2029-14.2014 · Cited by 213 · see citing works
Mani, K. M., Lefèbvre, C., Wang, K., Lim, W. K., Basso, K., Dalla‐Favera, R., & Califano, A. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.2 · Cited by 205 · see citing works
Self-citationChen, J. C., Alvarez, M. J., Talos, F., Dhruv, H., Rieckhof, G. E., Iyer, A., Diefes, K. L., Aldape, K., Berens, M., Shen, M. M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.021 · Cited by 188 · see citing works
Self-citationOperant alcohol self-administration in dependent rats: Focus on the vapor model
Vendruscolo, L. F., & Roberts, A. J. (2014) · Alcohol · doi:10.1016/j.alcohol.2013.08.006 · Cited by 166 · see citing works
Self-citationZhao, X., Arca, D. D., Lim, W. K., Brahmachary, M., Carro, M. S., Ludwig, T. E., Cardó, C. C., Guillemot, F., Aldape, K. D., Califano, A., et al. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.07.009 · Cited by 162 · see citing works
Self-citationGatta, G. D., Palomero, T., Pérez-García, A., Ambesi‐Impiombato, A., Bansal, M., Carpenter, Z., Keersmaecker, K. D., Solé, X., Xu, L., Paietta, E. M., et al. (2012) · Nature Medicine · doi:10.1038/nm.2610 · Cited by 146 · see citing works
Self-citationChudnovsky, Y., Kim, D., Zheng, S., Whyte, W. A., Bansal, M., Bray, M.-A., Gopal, S., Theisen, M. A., Bilodeau, S., Thiru, P., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2013.12.032 · Cited by 136 · see citing works
Self-citationERK regulation in chronic ethanol exposure and withdrawal
Sanna, P. P., Simpson, C., Lütjens, R., & Koob, G. F. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03191-8 · Cited by 134 · see citing works
Self-citationNader, K., & van der Kooy, D. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-01-00383.1997 · Cited by 133 · see citing works
VTA CRF neurons mediate the aversive effects of nicotine withdrawal and promote intake escalation
Grieder, T. E., Herman, M. A., Contet, C., Tan, L. A., Vargas-Pérez, H., Cohen, A., Chwalek, M., Maal‐Bared, G., Freiling, J., Schlosburg, J. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3872 · Cited by 132 · see citing works
Self-citationOperant Behavior and Alcohol Levels in Blood and Brain of Alcohol‐Dependent Rats
Gilpin, N. W., Smith, A. D., Cole, M., Weiss, F., Koob, G. F., & Richardson, H. N. (2009) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2009.01051.x · Cited by 122 · see citing works
Self-citationMPZP: A novel small molecule corticotropin-releasing factor type 1 receptor (CRF1) antagonist
RICHARDSON, H., ZHAO, Y., Fekete, É. M., FUNK, C., Wirsching, P., Janda, K. D., Zorrilla, E. P., & Koob, G. F. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.10.008 · Cited by 95 · see citing works
Self-citationFrancesconi, W., Berton, F., Repunte‐Canonigo, V., Hagihara, K., Thurbon, D., Lekić, D., Specio, S. E., Greenwell, T. N., Chen, S. A., Rice, K. C., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5129-08.2009 · Cited by 90 · see citing works
Self-citationNeuroplasticity in brain reward circuitry following a history of ethanol dependence
Hansson, A. C., Rimondini, R., Neznanova, O., Sommer, W. H., & Heilig, M. A. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06159.x · Cited by 84 · see citing works
Cho, K., & Little, H. J. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00264-4 · Cited by 75 · see citing works
Briand, L. A., Vassoler, F. M., Pierce, R. C., Valentino, R. J., & Blendy, J. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2827-10.2010 · Cited by 63 · see citing works
Morphine produces circuit-specific neuroplasticity in the bed nucleus of the stria terminalis
Dumont, É. C., Rycroft, B. K., Maiz, J., & Williams, J. T. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.039 · Cited by 42 · see citing works
EFFECT OF LOCAL INTRACEREBRAL CORTICOSTERONE IMPLANTS ON ALCOHOL INTAKE IN THE RAT
Fahlke, C. (1999) · Alcohol and Alcoholism · doi:10.1093/alcalc/34.6.851 · Cited by 37 · see citing works
Tye, S. J., Miller, A. D., & Blaha, C. D. (2009) · Synapse · doi:10.1002/syn.20682 · Cited by 20 · see citing works
ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1
Galbraith, M. D., Saxton, J., Li, L., Shelton, S. J., Zhang, H., Espinosa, J. M., & Shaw, P. E. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt837 · Cited by 15 · see citing works
Alvarez, M. J., Sumazin, P., Rajbhandari, P., & Califano, A. (2009) · Genome biology · doi:10.1186/gb-2009-10-12-r143 · Cited by 15 · see citing works
Self-citationCommentary: Systems biology and its relevance to alcohol research.
Guo, Q., & Zakhari, S. (2008) · PubMed · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [50]Expression profiling of brain structures of dependent and non-dependent rats self-administering alcohol and naive controls. NCBI Gene Expression Omnibus. See http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60966.
Cited by
Sorted by citations
Cell-type specialization is encoded by specific chromatin topologies
Winick‐Ng, W., Kukalev, A., Harabula, I., Zea-Redondo, L., Szabó, D., Meijer, M., Serebreni, L., Zhang, Y., Bianco, S., Chiariello, A. M., et al. (2021) · Nature · doi:10.1038/s41586-021-04081-2 · Cited by 205 · see citing works
The recurrent architecture of tumour initiation, progression and drug sensitivity
Califano, A., & Alvarez, M. J. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.124 · Cited by 198 · see citing works
Self-citationGenetic studies of alcohol dependence in the context of the addiction cycle
Reilly, M. T., Noronha, A., Goldman, D. A., & Koob, G. F. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.017 · Cited by 155 · see citing works
Self-citationIdentification of neurodegenerative factors using translatome–regulatory network analysis
Brichta, L., Shin, W., Jackson-Lewis, V., Blesa, J., Yap, E.-L., Walker, Z., Zhang, J., Roussarie, J.-P., Alvarez, M. J., Califano, A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4070 · Cited by 118 · see citing works
Self-citationDing, H., Douglass, E. F., Sonabend, A. M., Mela, A., Bose, S., Gonzalez, C., Canoll, P., Sims, P. A., Alvarez, M. J., & Califano, A. (2018) · Nature Communications · doi:10.1038/s41467-018-03843-3 · Cited by 118 · see citing works
Self-citationSomkuwar, S. S., Vendruscolo, L. F., Fannon, M. J., Schmeichel, B. E., Nguyen, T. B., Guevara, J., Sidhu, H., Contet, C., Zorrilla, E. P., & Mandyam, C. D. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.06.006 · Cited by 64 · see citing works
Self-citationAstrocyte-specific transcriptome responses to chronic ethanol consumption
Erickson, E. K., Farris, S. P., Blednov, Y. A., Mayfield, R. D., & Harris, R. A. (2018) · The Pharmacogenomics Journal · doi:10.1038/s41397-017-0012-2 · Cited by 56 · see citing works
Dysregulation of brain stress systems mediates compulsive alcohol drinking
Tunstall, B. J., Carmack, S. A., Koob, G. F., & Vendruscolo, L. F. (2017) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2016.10.006 · Cited by 55 · see citing works
Self-citationResetting the Stress System with a Mifepristone Challenge
Dalm, S., Karssen, A. M., Meijer, O. C., Belanoff, J. K., & de Kloet, E. R. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0614-5 · Cited by 47 · see citing works
Koob, G. F., & Vendruscolo, L. F. (2023) · Current topics in behavioral neurosciences · doi:10.1007/7854_2023_424 · Cited by 44 · see citing works
Self-citationOncoLoop: A Network-Based Precision Cancer Medicine Framework
Vasciaveo, A., Arriaga, J. M., de Almeida, F. N., Zou, M., Douglass, E. F., Picech, F., Shibata, M., Rodríguez-Calero, A., de Brot, S., Mitrofanova, A., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0342 · Cited by 38 · see citing works
Self-citationFinn, D. A., Hashimoto, J. G., Cozzoli, D. K., Helms, M. L., Nipper, M. A., Kaufman, M. N., Wiren, K. M., & Guizzetti, M. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00325 · Cited by 40 · see citing works
Savarese, A., Ozburn, A., Metten, P., Schlumbohm, J. P., Hack, W. R., LeMoine, K., Hunt, H., Hausch, F., Bauder, M., & Crabbe, J. (2020) · Alcoholism: Clinical and Experimental Research · doi:10.1111/acer.14318 · Cited by 34 · see citing works
Glucocorticoid receptor modulators decrease alcohol self-administration in male rats
McGinn, M. A., Tunstall, B. J., Schlosburg, J. E., Gregory-Flores, A., George, O., de Guglielmo, G., Mason, B. J., Hunt, H. J., Koob, G. F., & Vendruscolo, L. F. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108510 · Cited by 35 · see citing works
Self-citationOff-label and investigational drugs in the treatment of alcohol use disorder: A critical review
Fischler, P. V., Soyka, M., Seifritz, E., & Mutschler, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.927703 · Cited by 34 · see citing works
Mechanisms of Alcohol Addiction: Bridging Human and Animal Studies
Kramer, J., Dick, D. M., King, A. C., Ray, L. A., Sher, K. J., Vena, A. A., Vendruscolo, L. F., & Ación, L. (2020) · Alcohol and Alcoholism · doi:10.1093/alcalc/agaa068 · Cited by 32 · see citing works
Self-citationBehavioral sensitization of the reinforcing value of food: What food and drugs have in common
Temple, J. L. (2016) · Preventive Medicine · doi:10.1016/j.ypmed.2016.06.022 · Cited by 31 · see citing works
11β-hydroxysteroid dehydrogenase inhibition as a new potential therapeutic target for alcohol abuse
Sanna, P. P., Kawamura, T., Chen, J., Koob, G. F., Roberts, A. J., Vendruscolo, L. F., & Repunte‐Canonigo, V. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.13 · Cited by 25 · see citing works
Self-citationThe prefrontal cortex as a critical gate of negative affect and motivation in alcohol use disorder
Pahng, A. R., McGinn, M. A., Paulsen, R. I., & Edwards, S. (2017) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2016.11.004 · Cited by 24 · see citing works
Khom, S., Rodriguez, L., Gandhi, P., Kirson, D., Bajo, M., Oleata, C. S., Vendruscolo, L. F., Mason, B. J., & Roberto, M. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105610 · Cited by 23 · see citing works
Self-citationMifepristone decreases chronic voluntary ethanol consumption in Rhesus macaques
Jimenez, V. A., Walter, N. A. R., Shnitko, T. A., Newman, N., Diem, K., Vanderhooft, L., Hunt, H., & Grant, K. A. (2020) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.120.000169 · Cited by 20 · see citing works
MR/GR Signaling in the Brain during the Stress Response
de Kloet, E. R., & Meijer, O. C. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.87234 · Cited by 19 · see citing works
de Carvalho, L. M., Wiers, C. E., Sun, H., Wang, G., & Volkow, N. D. (2020) · Brain and Behavior · doi:10.1002/brb3.1961 · Cited by 20 · see citing works
Applying the new genomics to alcohol dependence
Farris, S. P., Pietrzykowski, A. Z., Miles, M. F., O'Brien, M. A., Sanna, P. P., Zakhari, S., Mayfield, R. D., & Harris, R. A. (2015) · Alcohol · doi:10.1016/j.alcohol.2015.03.001 · Cited by 19 · see citing works
Self-citationde Guglielmo, G., Fu, Y., Chen, J., Larrosa, E., Hoang, I. B., Kawamura, T., Lorrai, I., Zorman, B., Bryant, J., George, O., et al. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146502 · Cited by 18 · see citing works
Self-citationInvestigational drug therapies in phase I and phase II clinical trials for alcohol use disorders
Walker, L. C., & Lawrence, A. J. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1502269 · Cited by 18 · see citing works
Differential regulation of alcohol consumption and reward by the transcriptional cofactor LMO4
Maiya, R., Pomrenze, M. B., Tran, T. N. A., Tiwari, G. R., Beckham, A., Paul, M. T., Mayfield, R. D., & Messing, R. O. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0706-8 · Cited by 17 · see citing works
Unveiling the Pathogenesis of Psychiatric Disorders Using Network Models
Zuo, Y., Don, W., Zhu, C., Naveed, O., Hong, W., & Yang, X. (2021) · Genes · doi:10.3390/genes12071101 · Cited by 17 · see citing works
Laise, P., Bosker, G., Sun, X., Shen, Y., Douglass, E. F., Karan, C., Realubit, R. B., Pampou, S., Califano, A., & Alvarez, M. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.12.091256 · Cited by 16 · see citing works
Self-citationKisby, B. R., Farris, S. P., McManus, M. M., Varodayan, F. P., Roberto, M., Harris, R. A., & Ponomarev, I. (2021) · Brain Sciences · doi:10.3390/brainsci11091149 · Cited by 15 · see citing works
Evaluation of mifepristone effects on alcohol-seeking and self-administration in baboons.
Holtyn, A. F., & Weerts, E. M. (2018) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000246 · Cited by 15 · see citing works
Tunstall, B. J., Lorrai, I., McConnell, S. A., Gazo, K. L., Zallar, L. J., de Guglielmo, G., Hoang, I. B., Haass‐Koffler, C. L., Repunte‐Canonigo, V., Koob, G. F., et al. (2019) · Alcohol and Alcoholism · doi:10.1093/alcalc/agz054 · Cited by 15 · see citing works
Self-citationWithdrawal from Brief Repeated Alcohol Treatment in Adolescent and Adult Male and Female Rats
Fleming, W., Jones, Q., Chandra, U., Saini, A., Walker, D. W., Francis, R., Ocampo, G., & Kuhn, C. M. (2018) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13936 · Cited by 14 · see citing works
A conceptual framework for the intersection of hyperalgesia and hyperkatifeia in alcohol addiction
Koob, G. F., & Vendruscolo, L. F. (2025) · Alcohol · doi:10.1016/j.alcohol.2025.08.004 · Cited by 14 · see citing works
Self-citationKhom, S., Borgonetti, V., Vozella, V., Kirson, D., Rodriguez, L., Gandhi, P. J., Bianchi, P., Snyder, A. E., Vlkolinský, R., Bajo, M., et al. (2023) · Neurobiology of Stress · doi:10.1016/j.ynstr.2023.100547 · Cited by 12 · see citing works
Cell-type specialization in the brain is encoded by specific long-range chromatin topologiesPreprint
Winick‐Ng, W., Kukalev, A., Harabula, I., Redondo, L. Z., Szabó, D., Meijer, M., Serebreni, L., Zhang, Y., Bianco, S., Chiariello, A. M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.02.020990 · Cited by 11 · see citing works
Drug addiction co-morbidity with alcohol: Neurobiological insights
McGinn, M. A., Pantazis, C. B., Tunstall, B. J., Marchette, R. C. N., Carlson, E. R., Said, N., Koob, G. F., & Vendruscolo, L. F. (2021) · International review of neurobiology · doi:10.1016/bs.irn.2020.11.002 · Cited by 9 · see citing works
Self-citationAlcohol Use Disorder: Stress, Negative Reinforcement, and Negative Urgency
Vendruscolo, L. F., Koob, G. F., & Zorrilla, E. P. (2023) · Springer eBooks · doi:10.1007/978-3-031-32483-3_36 · Cited by 8 · see citing works
Self-citationSavarese, A. M., Grigsby, K. B., Jensen, B. E., Borrego, M. B., Finn, D. A., Crabbe, J. C., & Ozburn, A. R. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.821859 · Cited by 8 · see citing works
Single-cell based elucidation of molecularly-distinct glioblastoma states and drug sensitivityPreprint
Ding, H., Burgenske, D. M., Zhao, W., Subramaniam, P. S., Bakken, K. K., He, L., Alvarez, M. J., Laise, P., Paull, E., Spinazzi, E. F., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/675439 · Cited by 8 · see citing works
Self-citationNeuroendocrinology meets addiction: Emerging pharmacotherapies on the horizon
Loftén, A., Farokhnia, M., Vendruscolo, L. F., & Leggio, L. (2025) · Journal of Internal Medicine · doi:10.1111/joim.70021 · Cited by 7 · see citing works
Self-citationDysregulation of c-Jun N-terminal kinase phosphorylation in alcohol dependence
Pahng, A. R., Paulsen, R. I., McGinn, M. A., Farooq, M. A., Edwards, K. N., & Edwards, S. (2018) · Alcohol · doi:10.1016/j.alcohol.2018.04.006 · Cited by 7 · see citing works
Fu, Y., Lorrai, I., Zorman, B., Mercatelli, D., Shankula, C. A., Gaytan, J. M., Lefèbvre, C., de Guglielmo, G., Kim, H. R., Sumazin, P., et al. (2022) · Viruses · doi:10.3390/v14040669 · Cited by 4 · see citing works
Self-citationNeurobiology of negative reinforcement as a driving force in alcohol addiction
Vendruscolo, L. F., & Koob, G. F. (2026) · Neuron · doi:10.1016/j.neuron.2026.04.038 · Cited by 4 · see citing works
Self-citationA survey of disease connections for CD4+ T cell master genes and their directly linked genes
Li, W., Enríquez, J. E., Simpfendorfer, K. R., & Lemus, E. H. (2015) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2015.08.009 · Cited by 3 · see citing works
Drawbacks to strengthening neural salience encoding: a link between cortisol and risky drinkingPreprint
Harris, B. B., Sinha, R., & Goldfarb, E. V. (2024) · doi:10.31234/osf.io/kht4d · Cited by 2 · see citing works
Hauser, S. R., Ferguson, L. B., Liang, T., Jarvis, E., Mayfield, R. D., & Bell, R. L. (2025) · Frontiers in Epigenetics and Epigenomics · doi:10.3389/freae.2024.1503093 · Cited by 1 · see citing works
Drawbacks to Strengthening Neural Salience Encoding: A Link Between Cortisol and Risky Drinking
Harris, B. B., Sinha, R., & Goldfarb, E. V. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1027-24.2024 · Cited by 4 · see citing works
(2021) · Elsevier eBooks · doi:10.1016/b978-0-12-816793-9.00001-3
Lorrai, I., Maccioni, R., Torres, I., Puliga, R., Gaytan, J. M., Giorgi, F. M., Repunte‐Canonigo, V., & Sanna, P. P. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.15.688629
Self-citationPathway-Level Synthesis Reveals Contrast-Dependent Rat Brain Transcriptomic Responses to Alcohol
An, H., Yu, J., Shao, C., Meng, D., Yang, G., & Wang, Z. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198873
- Authors
- Repunte-Canonigo, V., Shin, W., Vendruscolo, L. F., Lefebvre, C., van der Stap, L., Kawamura, T., Schlosburg, J. E., Alvarez, M., Koob, G. F., Califano, A., & Sanna, P. P.
- Affiliations
- Herbert Irving Comprehensive Cancer Center (US)
- Scripps Research Institute (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Califano, Andrea
- Sanna, Pietro Paolo
- ORCID
- Venue
- Genome Biology
- Published
- 2015-02-02
- Volume
- 16
- Issue
- 1
- Pages
- 68-68
- ISSN
- 1465-6906 (ISSN-L)
- PMC
- PMC4410476
- OpenAlex
- W2129957034
- Cited by
- 52
- References
- 52
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 4 · 2018: 8 · 2017: 2 · 2016: 6 · 2015: 3
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- National Institutes of Health (CA121852, AA017371, AA020960)
- National Institute on Alcohol Abuse and Alcoholism (R01AA017371, AA021667, R01AA021667, AA017371, AA020960, U01AA020960)
- National Heart, Lung, and Blood Institute (HL111566, U01HL111566)
- National Institute on Drug Abuse (R01DA013821, DA013821)
- National Cancer Institute (U54CA121852, U01CA168426, CA121852-09, CA1968426)
- National Institute on Deafness and Other Communication Disorders
- National Institute of General Medical Sciences (GM085659, R01GM085659, T32GM008798)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- alcoholism, excessive alcohol drinking, gene regulatory networks, transcriptional regulatory networks, glucocorticoid receptor, mifepristone, protracted abstinence, relapse, alcohol self-administration, brain reward system, stress system, medial prefrontal cortex, nucleus accumbens, central amygdala, ventral tegmental area, neural adaptation
- MeSH terms
- Ethanol, Alcoholism, Algorithms, Animals, Brain, Genes, Regulator, Hormone Antagonists, Receptors, Glucocorticoid, Self Administration, Mifepristone, Rats, Gene Regulatory Networks
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
