Research

The NIAAA is the lead agency for U.S. research on the causes, consequences, prevention and treatment of alcohol use disorder and alcohol-related problems.

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Laboratory on Neurobiology of Compulsive Behaviors (LNCB)

LNCB banner is a group picture of laboratory members in August 2022

Contact Information

Overview of the Lab

The Laboratory on Neurobiology of Compulsive Behaviors is a Joint Laboratory of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute of Mental Health (NIMH) led by Dr. Veronica Alvarez.

The Alvarez laboratory aims to understand the causes of substance use disorder (SUD). More specifically, we focus on the neuronal mechanisms that drive the high motivation to consume substances of abuse in SUD, and the compulsive aspects of SUD that generate a loss of control over consumption. Given that only a portion of individuals who are exposed to substances of abuse develop SUD, we are particularly interested in understanding the mechanisms that create vulnerability to SUD. The long-term goal of this research is to improve the treatment and prevention of SUD.

Our recent studies suggest that the behaviors characterizing SUD may develop from an interaction between the effects of substances of abuse and the individual’s pre-existing neurobiology. To further probe this hypothesis, we are investigating the synaptic and circuit mechanisms that mediate reward-seeking, reinforcement, and the loss of control over consumption.  We are carrying out a wide array of behavioral analysis and in vivo manipulations of neuronal activity to dissect the alterations to brain circuit function associated with SUD behaviors. Moreover, we are taking advantage of the individual variability of wild-type mice and leveraging the power of genetically engineered mouse models to understand what makes some brains more vulnerable to develop compulsive behaviors toward abused substances.

Lab Members

Selected Publications

Search for all publications from the Alvarez Lab on PubMed
 

D.A. Burke and V.A. Alvarez (2022) Serotonin receptors contribute to dopamine depression of lateral inhibition in the nucleus accumbens. Cell Reports 39(6):110795.

Razidlo, Fausner, Ingebretson, Wang, Petersen, Mirza, Swank, V.A. Alvarez and J.C. Lemos (2022) Chronic loss of muscarinic M5 receptor function manifests disparate impairments in exploratory behavior in male and female mice despite common dopamine regulation. Journal of Neuroscience

Markovic, Pedersen, Massaly, Vachez, Ruyle, Murphy, Abiraman, J.H. Shin, Garcia, Yoon, V.A. Alvarez, M.R. Bruchas, M Creed, J.A. Morón. (2021) Pain induces somatic adaptations in Ventral Tegmental Area Dopamine neurons to drive anhedonia-like behavior. Nature Neuroscience 24(11):1601—1613.

Al-Hasani, Gowrishankar, Schmitz, Pedersen, Marcus, Shirley, Hobbs, Elerding, Renaud, Jing, Y Li, V.A. Alvarez, J.C. Lemos and M.R. Bruchas (2021) Ventral tegmental area GABAergic inhibition of cholinergic interneurons in the ventral nucleus accumbens shell promotes reward reinforcement. Nature Neuroscience, 24(10):1414—1428.

Unger, Keller, Altermatt, Liang, Matsui, Dong, Hon, Yao, Sun, Banala, Flanigan, Jaffe, Hartanto, Carlen, Mizuno, Borden, Shivange, Cameron, Sinning, Underhill , Olson, Amara, Temple Lang, Rudnick, Marvin, Lavis, Lester, V.A. Alvarez, Fisher, Prescher, Kash, Yarov-Yarovoy, Gradinaru, LL Looger, L Tian (2020) Directed Evolution of a Selective and Sensitive Serotonin Sensor via Machine Learning. Cell 183(7):1986—2002.

M.F. Adrover, J.H. Shin, C. Quiroz, S. Ferré, J.C. Lemos, V.A. Alvarez (2020) Prefrontal Cortex-Driven Dopamine Signals in the Striatum Show Unique Spatial and Pharmacological Properties. Journal of Neuroscience 40(39), 7510—7522.

L.R. Halladay, A. Kocharian, P.T. Piantadosi, M.E. Authement, A.G. Lieberman, N.A. Spitz, K. Coden, L.R. Glover, V.D Costa, V.A. Alvarez, A. Holmes (2020) Prefrontal Regulation of Punished Ethanol Self-administration. Biological Psychiatry 87(11), 967—978.

Y. Ehinger, N. Morisot, S.A. Sakhai, K. Phamluong, M.F. Adrover, V.A. Alvarez, D Ron (2021) cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use. Neuropsychopharmacology 46(2), 334—342.

K. LeBlanc, T. London, Ilona Szczot, M.E. Bocarsly, D. Friend, K. Nguyen, M. Mengesha, M. Rubinstein, V.A. Alvarez and A. Kravitz (2020) Striatopallidal neurons control avoidance behavior in exploratory tasks. Molecular Psychiatry 25(2), 491—505.

M.E. Bocarsly, D. da Silva e Silva, V. Kolb, K.D. Luderman, S. Shashikiran, M. Rubinstein, D.R. Sibley, L.K. Dobbs, V.A. Alvarez (2019) A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors. Cell Reports 29(5):1147—1163.e5.

J.C. Lemos, J.H. Shin, V.A. Alvarez (2019) Striatal Cholinergic Interneurons Are a Novel Target of Corticotropin Releasing Factor. J Neurosci 39(29):5647—5661.

L.K. Dobbs, A.R. Kaplan, R. Bock, K. Phamluong, J.H. Shin, M.E. Bocarsly, L. Eberhart, D. Ron, V.A. Alvarez (2019) D1 Receptor Hypersensitivity in Mice With Low Striatal D2 Receptors Facilitates Select Cocaine Behaviors. Neuropsychopharmacology, 44(4):805—816.

A. Matsui, V.A. Alvarez (2018) Cocaine inhibition of synaptic transmission in the ventral pallidum is pathway-specific and medidated by serotonin. Cell Report 23(13), 3852–3863.

K.H. LeBlanc, T.D. London, I. Szczot, M.E. Bocarsly, D.M. Friend, K.P. Nguygen, M.M. Mengesha, M. Rubinstein, V.A. Alvarez, A.V. Kravitz (2018) Striatopallidal neurons control avoidance behavior in exploratory tasks. Molecular Psychiatry (epub ahead of print doi:10.1038/s41380-018-0051-3).

D.M. Friend, K. Devarakonda, T.J. O'Neal, M. Skirzewski, I. Papazoglou, A. Kaplan, J.S.Liow, S.G. Rane, M. Rubinstein, V.A. Alvarez, K.D. Hall, A.V. Kravitz. (2018) Basal ganglia dysfunction contributes to physical inactivity in obesity. Cell Metabolism 25(2), 312–321.

D.M. Lovinger, V.A. Alvarez (2017) Alcohol and basal ganglia circuitry: Animal models. Neuropharmacology 122, 46–55.

A. Matsui, V.A. Alvarez (2017) Undercover Power of Endocannabinoids: Postsynaptic Ion-Channel Modulator. Neuron 93(6), 1243–1244.

M.A. Hutchison, X. Gu, M.F. Adrover, M.R. Lee, T.S. Hnasko, V.A. Alvarez, W. Lu (2017) Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior. Mol. Psychiatry advanced online publication 14 February 2017; doi:10.1038/mp.2017.7.

P. Charbogne, O. Gardon, E. Martín-García, H.L. Keyworth, A. Matsui, A.E. Mechling, T. Bienert, T. Nasseef, A. Robé, L. Moquin, E. Darcq, S. Ben Hamida, P. Robledo, A. Matifas, K. Befort, C. Gavériaux-Ruff, L.A. Harsan, D. von Elverfeldt, J. Hennig, A. Gratton, I. Kitchen, A. Bailey, V.A. Alvarez, R. Maldoado, B.L. Kiefer (2017) Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food. Biol. Psychiatry 81(9):778–788.

D.M. Friend, K. Devarakonda, T.J. O'Neal, M. Skirzewski, I. Papazoglou, A.R. Kaplan, J.S. Liow, J. Guo, S.G. Rane, M. Rubinstein, V.A. Alvarez, K.D. Hall, A.V. Kravitz (2017) Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity. Cell Metab. 25(2), 312–21.

L.K Dobbs, J.C. Lemos, V.A. Alvarez (2017) Restructuring of basal ganglia circuitry and associated behaviors triggered by low striatal D2 receptor expression: implications for substance use disorders. Genes Brain Behav. 16(1), 56–70.

J.C. Lemos, D.M. Friend, A.R. Kaplan, J.H. Shin, M. Rubinstein, A.V. Kravitz, V.A. Alvarez (2016) Enhanced GABA Transmission Drives Bradykinesia Following Loss of Dopamine D2 Receptor Signaling. Neuron 90(4), 824–38.

L.K Dobbs, A.R. Kaplan, J.C. Lemos, A. Matsui, M. Rubinstein, V.A. Alvarez (2016) Dopamine Regulation Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine. Neuron 90(5), 1100–13.

V.A. Alvarez (2016) Clues on the coding of reward cues by the nucleus accumbens. PNAS USA 113(10, 2560–2.

J.H. Shin, M.F. Adrover, J. Wess, V.A. Alvarez (2015) Muscarinic regulation of dopamine and glutamate transmission in the nucleus accumbens. PNAS USA 112(26), 8124–9.

K.B. Holroyd, M.F. Adrover, R.L. Fuino, R. Bock, A.R. Kaplan, C.M. Gremel, M. Rubinstein, V.A. Alvarez (2015). Loss of feedback inhibition via D2 autoreceptors enhances acquistion of cocaine taking and reactivity to drug-paired cues. Neurophsychopharm advanced online publication 21 January 2015; doi: 10.1038/npp.2014.336.

M.F. Adrover, J.H. Shin, and V.A. Alvarez (2014). Glutamate and dopamine transmission from midbrain dopamine neurons share similar release properties but are differentially affected by cocaine. J. Neurosci. 34 (9), 3183–3192.

C. Cui, A. Noronha, H. Morikawa, V.A. Alvarez, G.D. Stuber, K.K. Szumlinski, T.L. Kash, M. Roberto, and M.V. Wilcox (2013). New insights on neurobiological mechanisms underlying alcohol addiction. Neuropharmacology 67:223–232.

M.V. Wilcox, V.C. Cuzon Carlson, N. Sherazee, G.M. Sprow, R. Bock, T.E. Thiele, D.M. Lovinger, and V.A. Alvarez (2014). Repeated binge-like ethanol drinking alters ethanol drinking patterns and depresses striatal GABAergic transmission. Neuropsychopharmacology 39(3):579–594.

R. Bock, J.H. Shin, A.R. Kaplan, A. Dobi, E. Markey, P.F. Kramer, C.M. Gremel, C.H. Christensen, M.F. Adrover, and V.A. Alvarez (2013). Strengthening the accumbal indirect pathway promotes resilience to compulsive cocaine use. Nat. Neurosci. 16(5):632–638.

N. Sherazee, V.A. Alvarez (2013). DiOlistics: delivery of fluorescent dyes into cells. Methods Mol. Biol. 940:391–400.

A. Dobi, G.K. Seabold, C.H. Christensen, R. Bock, and V.A. Alvarez. (2011). Cocaine-Induced Plasticity in the Nucleus Accumbens Is Cell Specific and Develops without Prolonged Withdrawal. J. Neurosci. 31:1895–904.

P.F. Kramer, C.H. Christensen, L.A. Hazelwood, A. Dobi, R. Bock, D.R. Sibley, Y. Mateo, and V.A. Alvarez. (2011). Dopamine D2 receptor overexpression alters behavior and phsiology in Drd2-EGPFP mice. J. Neurosci. 31:126–32. Faculty of 1000 "Recommended" list.

E. Bello Gay, Y. Mateo, D.M. Gelman, D. Noaín, J.H. Shin, C.M. Bäckman, M.J. Low, V.A. Alvarez, D.M. Lovinger and M. Rubinstein (2011). Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors. Nature Neurosci. 14: 1033–8

V. Cuzon Carlson, G.K. Seabold, C.M. Helms, N. Garg, M. Odagiri, A.R. Rau, J. Daunais, and V.A. Alvarez, D.M. Lovinger and K.A. Grant (2011). Synaptic and morphological neuroadaptations in the putamen associated with long-term, relapsing alcohol drinking in primates. Neuropsychopharm. 36: 2513–28

B.N. Mathur, N.A. Capik, V.A. Alvarez, and D.M. Lovinger (2011). Serotonin induces long-term depression at corticostriatal synapses. J Neurosci. 31(20):7402–11.

M. Feyder, R.M. Karlsson, P. Mathur, M. Lyman, R. Bock, R. Momenan, J. Munasinghe, M.L. Scattoni, J. Ihne, M. Camp, C. Graybeal, D. Strathdee, V.A. Alvarez, P. Kirsch, M. Rietschel, S. Cichon, H. Walter, A. Meyer-Lichtenberg, S.G. Grant and A. Holmes. (2010). Association of mouse Dlg4 (PSD-95) gene deletion and human DLG4 gene variation with phenotypes relevant to autism spectrum disorders and Williams' syndrome. Am. J. Psychiatry 167:1508–17.

G.K. Seabold, J.B. Daunais, A. Rau, K.A. Grant, V.A. Alvarez. (2010). DiOLISTIC labeling of neurons from rodent and non-human primate brain slices. J. Vis. Exp. (41) pii:2081.

J.L. Brigman, T. Wright, G. Talani, S. Prasad-Mulcare, S. Jinde, G.K. Seabold, P. Mathur, M.I. Davis, R. Bock, R.M. Gustin, R.J. Colbran, V.A. Alvarez, K. Nakazawa, E. Delphire, D.M. Lovinger and A. Holmes. (2010). Loss of GluN2B-containing NMDA receptors in CA1 hippocampus and cortex impairs long-term depression, reduces dendritic spine density, and disrupts learning. J. Neurosci. 30:4590–600.

J. Cheng, X. Zhou, E.L. Miller, V.A. Alvarez, B.L. Sabatini, S.T. Wong. (2010). Oriented Markov random field based dendritic spine segmentation for fluorescence microscopy images. Neuroinformatics 8(3):157–70.

V.A. Alvarez , D.A. Ridenour and B.L. Sabatini. (2007). Distinct Structural and Ionotropic Roles of NMDA Receptors in Controlling Spine and Synapse Stability. J. Neurosci. 28:7365–76.

V.A. Alvarez and B.L. Sabatini. (2007) Anatomical and physiological plasticity of dendritic spines. Annu. Rev. Neurosci. 30:79–97.

V.A. Alvarez , D.A. Ridenour and B.L. Sabatini. (2006). Retraction of synapses and dendritic spines induced by off-target effects of RNA interference. J. Neurosci. 26:7820–5. Faculty of 1000 "Must Read" list.

S.F. Tavazoie*, V.A. Alvarez* , D.A. Ridenour, D.J. Kwiatkowski, B.L. Sabatini (2005). Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat Neurosci. 8, 1727–34. Faculty of 1000 "Recommended" list.

V.A. Alvarez , C. Chow, E.J. Van Bockstaele and J.T. Williams. (2002). Frequency-dependent synchronization of locus coeruleus neurons: role of electrotonic coupling. Proc Natl Acad Sci U S A . 99: 4032–6.

V.A. Alvarez *, S. Arttamangkul*, J. Whistler, M. van Zastrow, D. Grandy and J.T. Williams. (2002). mu-Opioid receptors: Ligand-dependent activation of potassium conductance, desensitization, and internalization. J Neurosci. 22: 5769–76.

V.A. Alvarez , S. Arttamangkul, and J.T. Williams. (2001). A RAVE about Opioid Withdrawal. Neuron 32: 761–763. New and Views.

V.A. Alvarez , Maubecin, F. Garcia-Hernandez, J.T. Williams and E. Van Bockstaele. (2000). Functional coupling between neurons and glia. J. Neurosci. 20: 4091–4098.

Other Lab Resources

NIH Resources

Collaborators

present
past

Alumni

Marlisa Shaw
Postbaccalaureate, IRTA
Fall 2020 – Spring 2022
currently MD/PhD student at Vanderbilt University.

Sean Hernandez
Postbaccalaureate, IRTA
Summer 2020 – Summer 2021
currently medical student at the Medical Collage of Wisconsin.
Aya Matsui, PhD

Aya Matsui, PhD
Postdoctoral IRTA
Fall 2013 – Fall 2020
currently at the Vollum Institute at OHSU in Oregon.

Wambura Fobbs, PhD
Postdoctoral IRTA
Spring 2019 – Summer 2020
Katie Teresi

Katie Teresi
Postbaccalaureate
Summer 2018 – Summer 2020
currently DO candidate at Tuoro University

Isabel Bleimeister
Postbaccalaureate, IRTA
Summer 2019 – Summer 2020
currently medical student at the University of Pittsburgh
Marilyn

Marylin Bravo
Postbaccalaureate, IRTA
Summer 2018 — Summer 2019
kathy dai

Kathy Dai
Postbaccalaureate, IRTA
Summer 2018 — Summer 2019
currently medical student at Duke University
Lauren Dobbs

Lauren Dobbs, PhD
Postdoctoral Fellow, IRTA
Summer 2012 — Winter 2018
currently Assistant Professor at the Waggoner Center for Alcohol & Addiction Research at The University of Texas at Austin
tanisha-london

Tanisha London, BSc
Postbaccalaureate IRTA
Fall 2017 — Summer 2018
currently graduate student University of Southern California (USC)
Sannidhi S.

Sannidhi Shashikiran
Volunteer
Sommer 2017 — Sommer 2018
currently college student at Georgetown University
Julia L.

Julia Lemos, PhD
Postdoctoral Fellow, IRTA
Summer 2012 — Winter 2017
currently Assistant Professor in the Medical Discovery Team Addiction at the MDT University of Minnesota
Martin A.

Martin Adrover, PhD
Postdoctoral Visiting Fellow
Winter 2010 — Fall 2017
currently faculty at INGEBI - CONICET in Buenos Aires, Argentina
Elizabeth kirby

Elizabeth Kirby
Lab Secretary
Mariah blegen

Mariah Blegen, BS
Postbaccalaureate IRTA
Summer 2013 — Summer 2015
currently a medical student at School of Medicine & Dentistry University of Rochester

 

Shan-He

He, PhD
Postdoctoral Visiting Fellow
Winter 2014 — Summer 2014
currently a industry researcher in Shanghai, China.
Alanna kaplan

Alanna Kaplan, BS
Postbaccalaureate IRTA
Summer 2011 — Summer 2013
currently a graduate student (MD/PhD) at Yale School of Medicine
JilianIafrati

Jilian Iafrati, PhD
Visting Fellow IRTA
Fall 2012 — Spring 2013
currently a post-doctoral fellow a University of California, San Francisco.
katie h

Katie Holroyd, BS
Postbaccalaureate IRTA
Spring 2012 — Spring 2013

currently a neurology resident at the Brigham and Women's Hospital & Massachusetts General Hospital
alice b.

Alice Dobi (Yue Wu), PhD
Postdoctoral Fellow
Summer 2008 — Summer 2012
currently a pathology resident at the PennState Health Milton S. Hershey Medical Center
Mark W.

Mark Wilcox, BS
Postbaccalaureate IRTA
Summer 2011 — Summer 2012

currently a Ob/Gyn resident at the University of California, San Francisco and
Co-founder and Director of MERIT (Medical Education Resources Initiative for Teens)
Robert F.

Robert Fuino, BS
Postbaccalaureate IRTA
Fall 2010 — Winter 2011

currently a neurology resident at the University of Vermont Medical Center
Nyssa

Nyssa Sherazee, BA
Postbaccalaureate IRTA
Spring 2010 — Summer 2011

currently a junior architect in New York
Paul K.

Paul Kramer, BA
Postbaccalaureate IRTA
Summer 2009 — Summer 2011
currently a post-doctoral fellow with Zayd Khaliq at NINDS
Eric M

Eric Markey, BA
Postbaccalaureate IRTA
Summer 2009 — Fall 2010
Gail S.

Gail Seabold, PhD
Postdoctoral Fellow, IRTA
Summer 2007 — Winter 2009
currently a Scientific Skill Coach at the Office of Intramural Training and Education (OITE) - seaboldg@mail.nih.gov
Christine C.

Christine Christensen, BS
Postbaccalaureate IRTA
Summer 2008 — 2009

currently a graduate student of nursing at the University of Alabama

Summer Students

Summer Internship Program in Biomedical Research (SIP) Amgen Scholars Program
Sannidhi Shashikiran 2017 Meredith Crenca 2017
Daniel Rosenberg 2012 Mariana Rocha 2017
Tracy Ma 2010 Vanessa Kolb 2016
Natasha Garg 2009 Lindsay Eberhart 2016
    Allisen Goncalves 2015
(CCSEP) Community College Summer Enrichment Program (HDTC) NINDS Health Disparities in Tribal Communities SIP
Gisselle Contreras 2022 Tawnjerae Joe 2018 & 2019
Amika Azinge 2021    
Carloyn Bowering 2017    
Michael Montesino 2014    

niaaa.nih.gov

An official website of the National Institutes of Health and the National Institute on Alcohol Abuse and Alcoholism

Looking for U.S. government information and services?
Visit USA.gov