Laboratory of Addictive Disorders
The major interest of the Laboratory of Addictive Disorders (LAD) is to unravel the neurobiological mechanisms of motivated behaviors. Research is focused on assessing the effects of exposure to rewards -including alcohol, drugs and palatable food- on behavior and brain function. The laboratory uses environmental and genetic animal models of disease, coupled to molecular biological and biochemical techniques.
Mission of LAD:
The LAD is committed to:
o Conduct research that expands our understanding of the pathophysiology and prevention of psychiatric diseases, and apply this to the development of novel therapeutics.
o Provide outstanding and multidisciplinary training to graduate and undergraduate students.
Dr. Sabino’s primary interests are to understand the neurobiological substrates of addiction to drugs of abuse -especially alcohol- as well as stress-related disorders and depression. An integrative behavioral, pharmacological and molecular approach is utilized to achieve the goals. The laboratory is working toward the development of new therapeutic agents to treat these psychiatric diseases. Current projects include exploring the role of the sigma receptor system in alcohol addiction and depression, and the investigation of the role of hypothalamic and extrahypothalamic neuropeptide systems in stress and anxiety.
Dr. Cottone’s research interests focus on the neurobiology of motivated behaviors and stress-related disorders. The major goal of Dr. Cottone’s research is identifying the biological bases of and potential treatments for eating disorders and obesity. Current projects evaluate the role of the corticotropin-releasing factor (CRF) and the endocannabinoid systems in compulsive eating and hedonic food intake. Dr. Cottone’s studies are carried out on environmental and genetic animal models, using behavioral, biochemical, and molecular approaches.
Pietro Cottone, Ph.D.
Associate Professor of Pharmacology and Psychiatry
Valentina Sabino, Ph.D.
Professor of Pharmacology and Psychiatry
Selected Peer-Reviewed Publications
Minnig MA, Park T, Echeveste Sanchez M, Cottone P, Sabino V. Viral-Mediated Knockdown of Nucleus Accumbens Shell PAC1 Receptor Promotes Excessive Alcohol Drinking in Alcohol-Preferring Rats. Front Behav Neurosci. 2021 Dec 3;15:787362.
Quadir SG, Tanino SM, Sami YN, Minnig MA, Iyer MR, Rice KC, Cottone P, Sabino V. Antagonism of Sigma-1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice. Alcohol Clin Exp Res. 2021 Jul;45(7):1398-1407. doi: 10.1111/acer.14635. Epub 2021 Jul 5. PMID: 34060104
Ferragud A, Velazquez-Sanchez C, Minnig MA, Sabino V, Cottone P. Pituitary adenylate cyclase-activating polypeptide (PACAP) modulates dependence-induced alcohol drinking and anxiety-like behavior in male rats. Neuropsychopharmacology. 2021 Feb;46(3):509-518. doi: 10.1038/s41386-020-00904-4. Epub 2020 Nov 16. PMID: 33191400
Hicks C, Sabino V, Cottone P. The Alpha-1 Adrenergic Receptor Antagonist Prazosin Reduces Binge-Like Eating in Rats. Nutrients. 2020 May 28;12(6):1569. doi: 10.3390/nu12061569. PMID: 32481494
Ferragud A, Velázquez-Sánchez C, Abdullatif AA, Sabino V, Cottone P. Withdrawal from Extended, Intermittent Access to A Highly Palatable Diet Impairs Hippocampal Memory Function and Neurogenesis: Effects of Memantine. Nutrients. 2020 May 23;12(5):1520. doi: 10.3390/nu12051520. PMID: 32456193
Quadir SG, Rohl CD, Zeabi A, Moore CF, Cottone P, Sabino V. Effect of different standard rodent diets on ethanol intake and associated allodynia in male mice. Alcohol. 2020 Sep;87:17-23. doi: 10.1016/j.alcohol.2020.04.003. Epub 2020 Apr 21. PMID: 32330590
Seiglie MP, Huang L, Cottone P, Sabino V. Role of the PACAP system of the extended amygdala in the acoustic startle response in rats. Neuropharmacology. 2019 Dec 1;160:107761. doi: 10.1016/j.neuropharm.2019.107761. Epub 2019 Sep 4. PMID: 31493466
Moore CF, Blasio A, Sabino V, Cottone P. Impulsive choice does not predict binge-like eating in rats. Behav Pharmacol. 2018 Dec;29(8):726-731. doi: 10.1097/FBP.0000000000000446. PMID: 30325787
Moore CF, Sabino V, Cottone P. Trace Amine Associated Receptor 1 (TAAR1) Modulation of Food Reward. Front Pharmacol. 2018 Feb 27;9:129. doi: 10.3389/fphar.2018.00129. PMID: 29535626
Moore CF, Sabino V, Koob GF, Cottone P. Neuroscience of Compulsive Eating Behavior. Front Neurosci. 2017 Aug 24;11:469. doi: 10.3389/fnins.2017.00469. PMID: 28883784
Velázquez-Sánchez C, Ferragud A, Moore CF, Everitt BJ, Sabino V, Cottone P. Neuropsychopharmacology. To the publication section, we will need two publications added: High Trait Impulsivity Predicts Food Addiction-Like Behavior in the Rat. 2014 Apr 29. doi: 10.1038/npp.2014.98. [Epub ahead of print] PMID: 24776685 .
Baiamonte BA, Valenza M, Roltsch EA, Whitaker AM, Baynes BB, Sabino V, Gilpin NW. Nicotine dependence produces hyperalgesia: role of corticotropin-releasing factor-1 receptors (CRF1Rs) in the central amygdala (CeA). Neuropharmacology. 2014 Feb;77:217-23. doi: 10.1016/j.neuropharm.2013.09.025. Epub 2013 Oct 6. PMID: 24107576
Blasio A, Iemolo A, Sabino V, Petrosino S, Steardo L, Rice KC, Orlando P, Arturo Iannotti F, Di Marzo V, Zorrilla EP, Cottone P. Rimonabant precipitates anxiety in rats withdrawn from palatable food: role of the central amygdale. Neuropsycholpharmacology. 2013 Jun 24. Epub ahead of print.
Sabino V, Narayan AR, Zeric T, Steardo L, Cottone P. mTOR activation is required for the anti-alcohol effect of ketamine, but not memantine, in alcohol-preferring rats. Behav Brain Res. 2013 Jun 15;247:9-16. PubMed PMID: 23466691; PubMed Central PMCID: PMC3646912.
Iemolo A, Blasio A, St Cyr SA, Jiang F, Rice KC, Sabino V, Cottone P. CRF-CRF1 Receptor System in the Central And Basolateral Nuclei Of The Amygdala Differentially Mediates Excessive Eating Of Palatable Food. Neuropsychopharmacology. 2013 Jun 10;PubMed PMID: 23748225.
Dore R, Iemolo A, Smith KL, Wang X, Cottone P, Sabino V. CRF Mediates the Anxiogenic and Anti-Rewarding, But Not the Anorectic Effects of PACAP. Neuropsychopharmacology.2013 May 9;PubMed PMID: 23657440.
Sabino V, Kwak J, Rice KC, Cottone P. Pharmacological characterization of the 20% alcohol intermittent access model in sardinian alcohol-preferring rats: a model of binge-like drinking. Alcohol Clin Exp Res. 2013 Apr;37(4):635-43. PubMed PMID: 23126554; PubMed Central PMCID: PMC3567206.
Cottone P, Sabino V, Nagy TR, Coscina DV, Levin BE, Zorrilla EP. Centrally administered urocortin 2 decreases gorging on high-fat diet in both diet-induced obesity-prone and -resistant rats. Int J Obes (Lond). 2013 Mar 12;PubMed PMID: 23478425.
Cottone P, Iemolo A, Narayan AR, Kwak J, Momaney D, Sabino V. The uncompetitive NMDA receptor antagonists ketamine and memantine preferentially increase the choice for a small, immediate reward in low-impulsive rats. Psychopharmacology (Berl). 2013 Mar;226(1):127-38. PubMed PMID: 23104264; PubMed Central PMCID: PMC3572289.
Blasio A, Steardo L, Sabino V, Cottone P. Opioid system in the medial prefrontal cortex mediates binge-like eating. Addict Biol. 2013 Jan 24;PubMed PMID: 23346966; PubMed Central PMCID: PMC3664255
Parylak SL, Cottone P, Sabino V, Rice KC, Zorrilla EP. Effects of CB1 and CRF1 receptor antagonists on binge-like eating in rats with limited access to a sweet fat diet: lack of withdrawal-like responses. Physiol Behav. 2012 Sep 10;107(2):231-42. PubMed PMID: 22776620.
Iemolo A, Valenza M, Tozier L, Knapp CM, Kornetsky C, Steardo L, Sabino V, Cottone P. Withdrawal from chronic, intermittent access to a highly palatable food induces depressive-like behavior in compulsive eating rats. Behav Pharmacol. 2012 Sep;23(5-6):593-602. PubMed PMID: 22854309.
Cottone P, Wang X, Park JW, Valenza M, Blasio A, Kwak J, Iyer MR, Steardo L, Rice KC, Hayashi T, Sabino V. Antagonism of Sigma-1 Receptors Blocks Compulsive-Like Eating Neuropsychopharmacology. 2012 Nov; 37(12);2593-604 . .
Blasio A, Narayan AR, Kaminski BJ, Steardo L, Sabino V, Cottone P. A modified adjusting delay task to assess implusive choice between isocaloric reinforcers in non-deprived male rats: effects of 5-HT2A/C and 5-HT1A receptor agonists. Psychopharmacology (Berl). 2012 Jan; 219(2):377-86.
Fekete EM, Zhao Y, Szücs A, Sabino V, Cottone P, Rivier J, Vale WW, Koob GF, Zorrilla EP. Systemic urocotrin 2, but not urocortin 1 or stressin 1-A, suppresses feeding via CRF2 receptors without malaise and stress. Br J Pharmacol. 2011 Dec; 164(8):1959-75.
Sabino V, Cottone P, Blasio A, Iyer MR, Steardo L, Rice KC, Conti B, Koob GF, Zorrilla EP. Activation of σ-receptor induces binge-like drinking in Sardinian alcohol-preferring rats. Neuropsychopharmacology. 2011 May; 36(6):1207-18. PMC 3079320. .
Repunte-Canonigo V, Berton F., Cottone P, Reifel-Miller A, Roberts AJ, Morales M., Francesconi W, Sanna PP. A potential role for adiponectin receptor 2 (AdipoR2) in the regulation of alcohol intake. Brain Res 2010 Jun 21; 1339:11-7. PMC2906226. .
Repunte-Canonigo V, van der Stap LD, Chen J, Sabino V, Wagner U, Zorrilla EP, Schumann G, Roberts AJ, Sanna PP. Genome-wide gene expression analysis identifies K-ras as a regulator of alcohol intake. Brain Res. 2010 Jun 21;1339: 1-10. PMC2925131..
Roberto M, Cruz MT, Gilpin NW, Sabino V, Schweitzer P, Bajo M, Cottone P, Madamba SG, Stouffer DF, Zorrilla EP, Koob GF, Siggins GF, Parson LH. Corticotropin releasing factor-induced amygdala gamma-aminobutyric Acid release play a key role in alcohol dependence. Biol Psychiatry. 2010 May 1; 67(9):831-9. PMC2883449. .
Cottone P, Sabino V, Roberto M, Bajo M, Pockros L, Frihauf J, Fekete EM, Steardo L, Rice KC, Grigoriadis D, Conti B, Koob GF, Zorrilla EP. CRF system recruitment mediates dark side of compulsive eating. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20016-20. PMC Journal 2785284
*The paper has been evaluated by the Faculty of 1000 Biology: 9, Excellent. Heilig, Markus .
Fonareva I, Spangler E, Cannella N, Sabino V, Cottone P, Ciccocioppo R, Zorrilla EP, Ryabinin AE. Increased perioculomotor Urocortin 1 immunoreactivity in genetically selected alcohol preferring rats. Alcohol Clin Exp Res. (2009); 33(11):1956-65. PMC 2813693..
Sabino V, Cottone P, Zhao Y, Steardo L, Koob GF, Zorrilla EP. Selective reduction of alcohol drinking in Sardinian alcohol-preferring rats by a sigma-1 receptor antagonist. Psychopharmacol 2009; 205(2): 327-335. PMC2748837
Greenwell TN, Funk CK, Cottone P, Richardson HN, Chen SA, Rice KC, Zorrilla EP, Koob GF. Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long-, but not short-access rats. Addiction Biology 2009 Apr;14(2):130-43. PMC2748834
Sabino V, Cottone P, Parylak SL, Steardo L, Zorrilla EP. Sigma-1 receptor knockout mice display a depressive-like phenotype. Behav Brain Res 2009; 198(2): 472-476. PMC2667953
Sabino V, Cottone P, Zhao Y, Iyer M, Steardo L yr, Steardo L, Rice KC, Conti B, Koob GF, Zorrilla EP. The sigma receptor antagonist BD-1063 decreases ethanol intake and reinforcement in animal models of excessive drinking. Neuropsychopharmacol 2009; 34(6): 1482-93. PMC2669694
Cottone P, Sabino V, Steardo L, Zorrilla EP. Consummatory, anxiety-related and metabolic adaptations in female rats with alternating access to preferred food. Psychoneuroendocrinol 2009; 34(1):38-49. PMCID: PMC3224792.
Greenwell TN, Walker BM, Cottone P, Zorrilla EP, Koob GF. The alpha(1) adrenergic receptor antagonist prazosin reduces heroin self-administration in rats with extended access to heroin administration. Pharmacol Biochem Behav. 2009; 91(3):295-302. PMC2637926
Cottone P, Sabino V, Steardo S, Zorrilla EP. Intermittent preferred food access reduces the reinforcing efficacy of chow in rats. Am J Physiol Regul Integr Comp Physiol 2008; 295(4):R1066-76. PMC2576087
Cottone P, Sabino V, Steardo L, Zorrilla EP. Opioid-dependent anticipatory negative contrast and binge-like eating in rats with limited access to highly preferred food. Neuropsychopharmacol 2008; 33(3):524-35. PMC Journal – In Process
George O, Ghozland S, Azar MR, Cottone P, Zorrilla EP, Parsons LH, O’Dell LE, Richardson HN, Koob GF. CRF-CRF1 system activation mediates withdrawal-induced anxiety-like behavior and increases in nicotine self-administration in nicotine dependent rats. Proc Natl Acad Sci 2007; 104(43):17198-203. PMC2040467
Cottone P, Sabino V, Nagy TR, Rivier JE, Coscina DV, Zorrilla EP. Feeding microstructure in diet-induced obesity susceptible and resistant rats: comparative central effects of urocortin 2. J Physiol 2007; 583(Pt 2):487-504. PMC2277029
Sabino V, Cottone P, Steardo L, Schmidhammer H, Zorrilla EP. 14-methoxymetopon, a highly potent mu opioid agonist, biphasically affects ethanol intake in Sardinian alcohol-preferring rats. Psychopharmacol 2007; 192(4):537-46. PMC Journal – In Process
Cottone P, Sabino V, Steardo L, Zorrilla EP. FG 7142 specifically reduces meal size and the rate and regularity of sustained feeding in female rats: evidence that benzodiazepine inverse agonists reduce food palatability. Neuropsychopharmacol 2007; 32(5):1069-81. PMC Journal – In Process
Sabino V, Cottone P, Koob GF, Steardo L, Lee MJ, Rice KC, Zorrilla EP. Dissociation between opioid and CRF1 antagonist sensitive drinking in Sardinian alcohol-preferring rats. Psychopharmacol 2006; 189(2):175-86. PMC Journal – In Process
Neurobiology of Compulsive Eating Presentation at The Royal Society’s “Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists.”
PsychCentral. New Pharmacological Approach for Binge Eating. Laboratory of Addictive Disorders identify new therapeutic approach.
Sciencedaily: Impulsivity is a risk factor for food addition.
Huffington Post: Could Impulsive Behavior Lead to Food Addiction?
Boston University School of Medicine. Researchers in the Laboratory of Addictive Disorders have discovered that impulsivity is a risk factor for food addiction . Results of the study, published online in Neuropsychopharmacology , suggest that impulsivity promotes pathological overeating.
NIDAIRP Hot Paper, November 2012: Antagonism of Sigma-1 Receptors Blocks Compulsive-Like Eating
Boston University School of Medicine:
BUSM Researchers Find Drug Used for Addiction Treatment May Block Binge Eating Impulse.
Yahoo! News: Addiction Drug Could Curb Binge Eating.
Forbes: Obesity’s Hazards And Mysteries
ScienceNow: Chocolate Cake: The New Heroin?
NIH, News in Health: Restricting Sugary Food May Backfire
BU Today: The Binge Eater as Junkie