M ETHODS IN M OLECULAR B IOLOGY

Series Editor John M. Walker School of Life and Medical Sciences University of Hertfordshire Hatfield, Hertfordshire, UK

For further volumes: http://www.springer.com/series/7651 For over 35 years, biological scientists have come to rely on the research protocols and methodologies in the critically acclaimed Methods in Molecular Biology series. The series was the first to introduce the step-by-step protocols approach that has become the standard in all biomedical protocol publishing. Each protocol is provided in readily-reproducible step-by- step fashion, opening with an introductory overview, a list of the materials and reagents needed to complete the experiment, and followed by a detailed procedure that is supported with a helpful notes section offering tips and tricks of the trade as well as troubleshooting advice. These hallmark features were introduced by series editor Dr. John Walker and constitute the key ingredient in each and every volume of the Methods in Molecular Biology series. Tested and trusted, comprehensive and reliable, all protocols from the series are indexed in Pub Med. Psychiatric Disorders

Methods and Protocols

Edited by Firas H. Kobeissy

Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Editor Firas H. Kobeissy Department of Biochemistry and Molecular Genetics Faculty of Medicine American University of Beirut Beirut, Lebanon

ISSN 1064-3745 ISSN 1940-6029 (electronic) Methods in Molecular Biology ISBN 978-1-4939-9553-0 ISBN 978-1-4939-9554-7 (eBook) https://doi.org/10.1007/978-1-4939-9554-7

© Springer Science+Business Media, LLC, part of Springer Nature 2019, corrected publication 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Cover Caption: The Brain: A Curious Tale of Chasing the Enigma “A hand stretched out beyond spiritual world in search for a stable ground. It landed at lab bench; unravelling an, otherwise, enigmatically whispering neurons and genome. Still, the odyssey never reaches destiny.” Cover designed by Dr. Samar Abdelhady, MD.

This Humana imprint is published by the registered company Springer Science+Business Media, LLC, part of Springer Nature. The registered company address is: 233 Spring Street, New York, NY 10013, U.S.A. Dedication

To my mentor and colleague, Professor Julnar Usta, whose sincere and honest devotion to research and teaching has touched many students, researchers, and medical doctors, I dedicate this humble work. I will always learn from her encyclopedic knowledge in Biochemistry...

v Foreword

According to the World Health Organization (WHO), an estimated one in six individuals, globally, suffers from neurological diseases, inclusive of mental, traumatic, neurodegenera- tive, and autoimmune disorders. In light of this and the tumultuous conditions of “conflict zones” and the fallout in terms of psychiatric disorders, drug abuse, poverty, and malnutri- tion, the second edition of Psychiatric Disorders provides a needed and timely roadmap for research. While much of the neuroscience community has been focused, of late, on neuro- degenerative conditions, it is refreshing to see a text that brings together unique expertise and state-of-the-art methodologies that will benefit seasoned researchers, as well as emerging generations of pioneers in the realm of psychiatric illness, mental disorders, and translational scientists. Firas Kobeissy has assembled a panel of experts to act as guides on this journey of discovery. The approach is systematic in introducing relevant preclinical models of pressing psychiatric conditions—from the classics of depression, anxiety, and substance abuse to more recently recognized post-traumatic stress disorder (PTSD), eating disorders, and the ever-elusive search for reliable validated diagnostic and prognostic biomarkers. Despite a focus on laboratory models, the translational relevance to the clinical setting is obvious, particularly for those focused on the development of effective intervention and therapeutic development. Also evident to the reader is the mechanistic quest that underlies each submission.

Approach

This volume introduces the novice and savvy researcher to an overview of key concerns in psychiatric disorder research and the state of this broad field before delving into the specifics of models and methodologies. Having fielded complaints from students and researchers on the paucity of translatable details in methods for, well, over 30 years, this volume is a welcome relief in providing much-needed details for validation of methods and serves the reader well in establishing the credibility of the generated data. This credibility is further enhanced by the choice of chapter authors, all of whom are recognized experts in their area. In addition, the editor does not monopolize the volume, which further distinguishes it as a “sincere” effort in publicizing the best of what the field has to offer. Sections of the volume tackle the details of psychiatric illness, substance abuse disorders, and eating disorders. However, its timeliness is underscored by cutting-edge research on biomarkers and “omic” approaches. Particularly attractive to this reader is the transdisciplin- ary approach that recognizes—indeed invites—collaborative approaches toward sustainable solutions, as well as setting the stage for a “benchtop to bedside” paradigm. Any seasoned researcher readily recognizes the challenges inherent between transitioning from animal models that address basic mechanisms, identify targets of diagnosis and intervention, and the ability to extrapolate to the human condition and clinical field. Most, if not all chapters in the volume, attempt to address such challenges, raising the value of these submissions in terms of relevance.

vii viii Foreword

Fig. 1 A cohesive roadmap towards translation and precision health

As one who is keen on promoting “Precision Health,” not just precision or personalized medicine, the intricate interplay between behavior, socioeconomics, gene-environment interaction, and effective diagnostics—possibly theranostics—the availability of a starting point that allows for integration of animal models, molecular mechanisms, and systems biology approach to data analytics holds much promise. The greater challenge, which is met to a great extent in this second edition, is how to not become so verbose as to lose sight of the desired benefit—the equipping of the researcher with the tools to effectively carry out quality applied research and articulate data in a meaningful way (Fig. 1).

Recommendation

This volume is an indispensable addition to any serious researcher’s bookshelf, physical or virtual. It is not likely to collect dust, as it provides hands-on know-how and shares that know-how not only to those focused on psychiatric disorders but also for the discerning neuroscientist seeking answers. With contributions on neuroplasticity, neurogenesis, assess- ment of cognitive decline, dyskinesia, tobacco use, environmental tobacco smoke (ETS), obesity-related behavior, PTSD, and deciphering frontiers in genomics, transcriptomics, and metabolomics, there is food for thought for those who recognized the interconnectedness of environment-neurobehavior and health outcomes.

Hassan A. N. El-Fawal Neuroscience, Pharmacology and Toxicology, School of Sciences and Engineering, Institute of Global Health and Human Ecology, The American University in Cairo, Cairo, Egypt Preface

As the of field neuroscience is evolving, newly discoveries at the cellular and molecular levels are revolutionizing the previous classical concepts into new developed understandings, paving the way for the development of new therapies, aiding in the diagnosis, and even proposing novel treatment modalities for psychiatric and neurological disorders. Some—if not most—of these discoveries have been made possible with the advent of experimental animal models. Experimental models that mimic human neuropsychiatric disorders have been described and optimized over the years to assist in understanding the pathogenesis and pathophysiology of psychiatric disorders and for the evaluation of therapies as well. Indeed, several of these models have significantly improved our understanding of the fundamental mechanisms of neuropsychiatric disorders, their development, and cure. Having said that, the need to optimize these experimental models, to correctly reproduce the findings and data generated, cannot be underestimated in order to translate into the clinical settings. Thus, providing researchers and scientists with well-detailed descriptions of the protocols applied in animal models will ultimately help them design their scientific questions and inquiries with ease and efficiency. These described protocols will also serve as a guide for students and postgraduates who are starting their scientific careers seeking learning novel techniques as well as novel models relevant to their research areas. Therefore, this second edition of the Psychiatric Disorders should be useful for gradu- ates, postdoctoral workers, as well as established scientists working in the fields of behavioral and molecular neuropsychiatric research. In this edition, we provide updates on the methods and protocols discussed in the first edition while still providing novel ones. As discussed in the first edition, we have invited top-notch neuroscience and psychiatry experts as well as physician scientists to write integrated chapters on recent updates in the neuropsychiatric research. In this book, authors and colleagues share their invaluable and insightful expertise and opinions. The collection of chapters here reflects the diversity and utility of animal models of psychiatric disorders, their development, establishment, and pathophysiological and molecular profile. In this book, we have included 39 chapters divided into 11 primary parts describing the protocols, techniques, methods, and different models applied in neuropsychiatric disorders. The first part consists of two chapters offering an overview of the experimental modeling of neuropsychiatric studies describing the usefulness and the need of animal models to relate the cellular and molecular changes occurring in human mental illnesses (Kaffman et al.). This is followed by a discussion chapter detailing the dilemma of the qualitative vs. quantitative nature of psychiatric research (Srivastava et al.). The second and third parts (consisting of eight chapters) are dedicated to experimental models of neuropsychiatric illnesses, including self-injurious behavior animal model, bipolar disorder, anxiety, learning, and decision-making testing as well as psychiatric illnesses and neurobehavioral injuries stemming from intoxication by metal elements and early-life adver- sity. The fourth and fifth parts (consisting of six chapters) discuss animal models of substance abuse. The fourth part discusses experimental models related to nicotine, alcohol, smoking, and methamphetamine abuse paradigms and techniques, while the fifth discusses the meth- ods used to develop these models as well as the techniques to assess their outcome and their ix x Preface effects. The sixth part (consisting of two chapters) discusses the detailed protocols to model animal models related to maladaptive eating habits and/or behaviors. The seventh and eight parts (consisting of nine chapters) focus on the animal models related mainly to neurodegenerative diseases stemming from natural causes (aging), aber- rant genetic background, or those induced by trauma. The chapters review and discuss how to design animal models needed to study neurodegenerative and behavioral consequences of aging, stroke, traumatic brain injury, epilepsy, and Leigh syndrome, while the ninth part (consisting of four chapters) discusses the inflammatory and metabolic alteration profiles relevant to neuropsychiatric disorders including autism spectrum disorders, depression, and other disorders. The last two parts (tenth and eleventh) consist of eight chapters integrating the genetic, epigenetic, and system biology approaches in the field of psychiatric disorders genetics, epigenetics, and systems biology in the field of psychiatric disorders. These chapters outline the novel approaches and molecular techniques needed to decipher and delineate topics in the areas of neuropsychiatric disorders. The tenth chapter focuses on the genetic studies of neuropsychiatric disorders, including Tic disorders and Tourette’s and Rett’s syndrome, providing protocols needed for the development and successful establishment of these genetic animal models. The last chapter focuses on the role of genetics and epigenetics in the development of psychiatric disorders and the use of molecular biology techniques, such as RT-PCR and chromatin immunoprecipitation, and high dimensionality data analytics and acquisition which are crucial for understanding the molecular mechanisms underlying such neuropsychiatric disorders. Finally, we hope that the chapters in this edition will benefit researchers in neuroscience and neuropsychiatric research. It is our hope that this book enables neuroscientists and psychiatrists to achieve success in their scientific endeavors and helps them solve several pending scientific questions with the most creative and insightful approaches.

Beirut, Lebanon Firas H. Kobeissy Acknowledgments

I would like to thank all the book authors and contributors for their valuable work; without their effort, I would have never finished this book. I am very grateful to Dr. Samar Abdelhady, who designed the attractive book art cover and tolerated my endless comments. Thank you.

xi Contents

Dedication ...... v Foreword...... vii Preface ...... ix Acknowledgments...... xi

PART IOVERVIEW OF THE ANIMAL RESEARCH IN PSYCHIATRIC ILLNESS

1 Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development ...... 3 Arie Kaffman, Jordon D. White, Lan Wei, Frances K. Johnson, and John H. Krystal 2 Qualitative vs. Quantitative Methods in Psychiatric Research: Updated ...... 23 A. Benjamin Srivastava, Firas H. Kobeissy, and Mark S. Gold

PART II OVERVIEW OF ANIMAL MODELS OF PSYCHIATRIC ILLNESS

3 Animal Models of Self-Injurious Behavior: An Update...... 41 Darragh P. Devine 4 Bipolar Disorder: Its Etiology and How to Model in Rodents ...... 61 Nadja Freund and Georg Juckel 5 Recent Updates in Modeling Risky Decision Making in Rodents ...... 79 Caitlin A. Orsini, Shelby L. Blaes, Barry Setlow, and Nicholas W. Simon

PART III METHODS OF ANIMAL MODELS OF PSYCHIATRIC ILLNESS

6 The Pemoline Model of Self-Injurious Behavior: An Update ...... 95 Darragh P. Devine 7 Rodent Models of Adaptive Value Learning and Decision-Making ...... 105 Alicia Izquierdo, Claudia Aguirre, Evan E. Hart, and Alexandra Stolyarova 8 The Visually Mediated Social Preference Test: A Novel Technique to Measure Social Behavior and Behavioral Disturbances in Zebrafish ...... 121 William H. J. Norton, Line Manceau, and Florian Reichmann 9 Animal Models of Intoxication by Metal Elements: A Focus on Neurobehavioral Injuries...... 133 Abdellatif Abbaoui, Lahcen Tamegart, and Halima Gamrani 10 Animal Models of Early-Life Adversity...... 143 Hajar Benmhammed, Samer El Hayek, Inssaf Berkik, Hicham Elmostafi, Rim Bousalham, Abdelhalem Mesfioui, Ali Ouichou, and Aboubaker El Hessni

xiii xiv Contents

PART IV OVERVIEW OF ANIMAL MODELS OF SUBSTANCE ABUSE

11 Nicotine Self-Administration as Paradigm for Medication Discovery for Smoking Cessation: Recent Findings in Medications Targeting the Cholinergic System...... 165 Jose M. Trigo and Bernard Le Foll 12 The Human Laboratory and Drug Development in Alcohol Use Disorder: Recent Updates ...... 195 Chidera C. Chukwueke and Bernard Le Foll 13 Rodent Models of Methamphetamine Misuse: Mechanisms of Methamphetamine Action and Comparison of Different Rodent Paradigms . 221 Hiba Hasan, Samar Abdelhady, Muhammad Haidar, Christina Fakih, Samer El Hayek, Stefania Mondello, Firas H. Kobeissy, and Abdullah Shaito

PART VMETHODS OF ANIMAL MODELS OF SUBSTANCE ABUSE

14 Recent Updates in Animal Models of Nicotine Withdrawal: Intracranial Self-Stimulation and Somatic Signs...... 253 Brandon Levin, Isaac Wilks, Sijie Tan, Azin Behnood-Rod, and Adriaan Bruijnzeel 15 Methods for Evaluating the Interaction Between Social Stress and Environmental Enrichment in Animal Models of Nicotine Addiction...... 267 Patricia Mesa-Gresa, Ara´nzazu Duque, Santiago Monleon, Concepcion Vinader-Caerols, and Rosa Redolat 16 An Animal Model of Alcohol Binge Drinking: Chronic-Intermittent Ethanol Administration in Rodents ...... 281 Santiago Monleon, Ara´nzazu Duque, Patricia Mesa-Gresa, Rosa Redolat, and Concepcion Vinader-Caerols

PART VI METHODS OF ANIMAL MODELS OF EATING DISORDERS

17 Animal Models of Eating Disorders ...... 297 Maria Scherma, Roberto Collu, Valentina Satta, Elisa Giunti, and Paola Fadda 18 Protocols Using Rodents to Model Eating Disorders in Humans ...... 315 Neil E. Rowland

PART VII REVIEW OF ANIMAL MODELS OF AGING,NEURODEGENERATIVE DISEASES AND TRAUMATIC BRAIN INJURY

19 Updates in PTSD Animal Models Characterization ...... 331 Lei Zhang, Xian-Zhang Hu, He Li, Xiaoxia Li, Tianzheng Yu, Jacob Dohl, and Robert J. Ursano Contents xv

20 Overview on Emotional Behavioral Testing in Rodent Models of Pediatric Epilepsy...... 345 Yasser Medlej, Houssein Salah, Lara Wadi, Sarah Saad, Rita Asdikian, Nabil Karnib, Dima Ghazal, Bashir Bashir, Jad Allam, and Makram Obeid

PART VIII METHODS OF ANIMAL MODELS OF AGING, NEURODEGENERATIVE DISEASES AND TRAUMATIC BRAIN INJURY

21 Neurological Exam in Rats Following Stroke and Traumatic Brain Injury...... 371 Hale Z. Toklu, Zhiui Yang, Mehmet Ersahin, and Kevin K. W. Wang 22 Y-Shaped Maze to Test Spontaneous Object Recognition and Temporal Order Memory After Traumatic Brain Injury...... 383 Hala Darwish and Hiba Hasan 23 An Animal Model to Test Reversal of Cognitive Decline Associated with Beta-Amyloid Pathologies ...... 393 Farah Deba, Steven Peterson, and Ayman K. Hamouda 24 Methods in Emotional Behavioral Testing in Immature Epilepsy Rodent Models ...... 413 Houssein Salah, Yasser Medlej, Nabil Karnib, Nora Darwish, Rita Asdikian, Sarah Wehbe, Ghadir Makki, and Makram Obeid 25 Methods in Electrode Implantation and Wiring for Long-Term Continuous EEG Monitoring in Rodent Models of Epilepsy and Behavioral Disturbances ...... 429 Yasser Medlej, Houssein Salah, Lara Wadi, Zahraa Atoui, Yasser Fadlallah, Rita Asdikian, Rana Bou Khalil, Rabih Hashash, and Makram Obeid 26 Behavior Model for Assessing Decline in Executive Function During Aging and Neurodegenerative Diseases...... 441 Brittney Yegla, Thomas C. Foster, and Ashok Kumar 27 Animal Model for Leigh Syndrome ...... 451 Sara El-Desouky, Yasmeen M. Taalab, Mohamed El-Gamal, Wael Mohamed, and Mohamed Salama

PART IX INFLAMMATORY AND METABOLIC PROFILES RELEVANT TO NEUROPSYCHIATRIC DISORDERS

28 Peripheral Biomarkers of Inflammation in Depression: Evidence from Animal Models and Clinical Studies ...... 467 J. P. Bra´s, S. Pinto, M. I. Almeida, J. Prata, O. von Doellinger, R. Coelho, M. A. Barbosa, and S. G. Santos 29 The Contribution of Inflammation to Autism Spectrum Disorders: Recent Clinical Evidence...... 493 J. Prata, A. S. Machado, O. von Doellinger, M. I. Almeida, M. A. Barbosa, R. Coelho, and S. G. Santos 30 Interleukin-2 and the Septohippocampal System: An Update on Intrinsic Actions and Autoimmune Processes Relevant to Neuropsychiatric Disorders ...... 511 Samer El Hayek, Farah Allouch, Luna Geagea, and Farid Talih xvi Contents

31 The Probiotic Mixture VSL#3 Reverses Olanzapine-Induced Metabolic Dysfunction in Mice ...... 531 Navneet Dhaliwal, Jatinder Dhaliwal, Dhirendra Pratap Singh, Kanthi Kiran Kondepudi, Mahendra Bishnoi, and Kanwaljit Chopra

PART XOVERVIEW AND METHODS OF GENETIC ANIMAL MODELS OF NEUROPSYCHIATRIC DISORDERS

32 Genetic Studies of Tic Disorders and Tourette Syndrome ...... 547 Yanjie Qi, Yi Zheng, Zhanjiang Li, Zhisheng Liu, and Lan Xiong 33 MeCP2 Dysfunction in Rett Syndrome and Neuropsychiatric Disorders ...... 573 Eunice W. M. Chin and Eyleen L. K. Goh 34 Behavioral Characterization of MeCP2 Dysfunction-Associated Rett Syndrome and Neuropsychiatric Disorders ...... 593 Eunice W. M. Chin and Eyleen L. K. Goh

PART XI ROLE OF GENETICS,MOLECULAR TECHNIQUES, AND EPIGENETICS IN NEUROPSYCHIATRIC DISORDERS

35 The Role of Epigenetics in Addiction: Clinical Overview and Recent Updates...... 609 Antoine Beayno, Samer El Hayek, Paul Noufi, Yara Tarabay, and Wael Shamseddeen 36 Chromatin Immunoprecipitation Techniques in Neuropsychiatric Research ...... 633 Andrew A. Bartlett and Richard G. Hunter 37 Chromatin Immunoprecipitation Assay for Analyzing Transcription Factor Activity at the Level of Peripheral Myelin Gene Promoters...... 647 Joelle Makoukji 38 Study of Myelin Gene Expression in the Central Nervous System Using Real-Time PCR...... 659 Diala El Khoury 39 Enhanced Molecular Appreciation of Psychiatric Disorders Through High-Dimensionality Data Acquisition and Analytics ...... 671 Jaana van Gastel, Jhana O. Hendrickx, Hanne Leysen, Bronwen Martin, Len Veenker, Sophie Beuning, Violette Coppens, Manuel Morrens, and Stuart Maudsley Correction to: Qualitative vs. Quantitative Methods in Psychiatric Research: Updated ...... C1

Index ...... 725 Contributors

ABDELLATIF ABBAOUI  Neurosciences, Pharmacology and Environment Unit, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh, Morocco SAMAR ABDELHADY  Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon CLAUDIA AGUIRRE  Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA JAD ALLAM  Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon FARAH ALLOUCH  Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon M. I. ALMEIDA  i3S-Instituto de Investigac¸a˜o e Inovac¸a˜o em Sau´ de, University of Porto, Porto, Portugal; INEB-Instituto de Engenharia Biome´dica, University of Porto, Porto, Portugal RITA ASDIKIAN  Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon ZAHRAA ATOUI  Faculty of Medicine, American University of Beirut, Beirut, Lebanon M. A. BARBOSA  i3S-Instituto de Investigac¸a˜o e Inovac¸a˜o em Sau´ de, University of Porto, Porto, Portugal; INEB-Instituto de Engenharia Biome´dica, University of Porto, Porto, Portugal; ICBAS-Instituto de Cieˆncias Biome´dicas Abel Salazar, University of Porto, Porto, Portugal ANDREW A. BARTLETT  Department of Psychology, University of Massachusetts Boston, Boston, MA, USA BASHIR BASHIR  Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon ANTOINE BEAYNO  Department of Psychiatry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon AZIN BEHNOOD-ROD  Department of Psychiatry, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL, USA HAJAR BENMHAMMED  Laboratory of Genetics, Neuroendocrinology, and Biotechnology, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco INSSAF BERKIK  Laboratory of Genetics, Neuroendocrinology, and Biotechnology, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco SOPHIE BEUNING  Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium MAHENDRA BISHNOI  National Agri-food Biotechnology Institute (NABI), Mohali, Punjab, India SHELBY L. BLAES  Department of Psychiatry, University of Florida, Gainesville, FL, USA RIM BOUSALHAM  Laboratory of Genetics, Neuroendocrinology, and Biotechnology, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco J. P. BRA´ S  i3S-Instituto de Investigac¸a˜o e Inovac¸a˜o em Sau´ de, University of Porto, Porto, Portugal; INEB-Instituto de Engenharia Biome´dica, University of Porto, Porto, Portugal; ICBAS-Instituto de Cieˆncias Biome´dicas Abel Salazar, University of Porto, Porto, Portugal ADRIAAN BRUIJNZEEL  Department of Psychiatry, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL, USA xvii xviii Contributors

EUNICE W. M. CHIN  Neuroscience and Mental Health Faculty, Lee Kong Chian School of Medicine, Nanyang Technology University, Singapore, Singapore KANWALJIT CHOPRA  Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Punjab University, Chandigarh, India CHIDERA C. CHUKWUEKE  Department of Pharmacology and Toxicology, King’s College Circle, University of Toronto, Toronto, ON, Canada R. COELHO  i3S-Instituto de Investigac¸a˜o e Inovac¸a˜o em Sau´ de, University of Porto, Porto, Portugal; FMUP-Faculty of Medicine, University of Porto, Porto, Portugal; Department of Clinical Neurosciences and Mental Health, Centro Hospitalar Universita´rio Sa˜o Joa˜o, Porto, Portugal ROBERTO COLLU  Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy VIOLETTE COPPENS  Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium NORA DARWISH  Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon HALA DARWISH  Hariri School of Nursing, Abu-Haidar Neuroscience Institute, American University of Beirut, Beirut, Lebanon; Department of Biochemistry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon FARAH DEBA  Department of Pharmaceutical Science, Fisch College of Pharmacy, University of Texas at Tyler, Tyler, TX, USA DARRAGH P. D EVINE  Department of Psychology, Behavioral and Cognitive Neuroscience Program, University of Florida, Gainesville, FL, USA JATINDER DHALIWAL  Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Punjab University, Chandigarh, India NAVNEET DHALIWAL  Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Punjab University, Chandigarh, India JACOB DOHL  Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Department of Military and Emergency Medicine, Consortium for Health and Military Performance, Uniformed Services University of the Health Sciences, Bethesda, MD, USA ARA´ NZAZU DUQUE  Universidad Internacional de Valencia, Valencia, Spain SARA EL-DESOUKY  Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura, Egypt MOHAMED EL-GAMAL  Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura, Egypt; Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; IUF—Leibniz Research Institute for Environmental Medicine, Du¨sseldorf, Germany SAMER EL HAYEK  Department of Psychiatry, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon ABOUBAKER EL HESSNI  Laboratory of Genetics, Neuroendocrinology, and Biotechnology, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco DIALA EL KHOURY  Department of Biology Louaize Lebanon, NDU Natural and Applied Sciences, Notre Dame University, Zouk Mosbeh, Lebanon HICHAM ELMOSTAFI  Laboratory of Genetics, Neuroendocrinology, and Biotechnology, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco Contributors xix

MEHMET ERSAHIN  Department of Neurosurgery, Istanbul Medeniyet University, Istanbul, Turkey PAOLA FADDA  Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy; Centre of Excellence “Neurobiology of Addiction”, University of Cagliari, Cagliari, Italy; CNR Institute of Neuroscience— Cagliari, National Research Council, Cagliari, Italy; National Neuroscience Institute, Cagliari, Italy YASSER FADLALLAH  Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon CHRISTINA FAKIH  Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon THOMAS C. FOSTER  McKnight Brain Institute, University of Florida, Gainesville, FL, USA NADJA FREUND  Division of Experimental and Molecular Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr- University, Bochum, Germany HALIMA GAMRANI  Neurosciences, Pharmacology and Environment Unit, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh, Morocco LUNA GEAGEA  Department of Psychiatry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon DIMA GHAZAL  Faculty of Sciences, Lebanese University, Beirut, Lebanon ELISA GIUNTI  Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy EYLEEN L. K. GOH  Neuroscience and Mental Health Faculty, Lee Kong Chian School of Medicine, Nanyang Technology University, Singapore, Singapore; Department of Research, National Neuroscience Institute, Singapore, Singapore; Neuroscience Academic Clinical Programme, Singhealth Duke-NUS Academic Medical Center, Singapore, Singapore MARK S. GOLD  Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA MUHAMMAD HAIDAR  Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon AYMAN K. HAMOUDA  Department of Pharmaceutical Science, Fisch College of Pharmacy, University of Texas at Tyler, Tyler, TX, USA EVAN E. HART  Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA HIBA HASAN  Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon RABIH HASHASH  Animal Care Facility, American University of Beirut, Beirut, Lebanon JHANA O. HENDRICKX  Receptor Biology Lab, Department of Biomedical Research, University of Antwerp, Antwerp, Belgium; Faculty of Pharmacy, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium XIAN-ZHANG HU  Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA RICHARD G. HUNTER  Department of Psychology, University of Massachusetts Boston, Boston, MA, USA; Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA ALICIA IZQUIERDO  Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA; The Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; Integrative Center for Learning and Memory, University of xx Contributors

California at Los Angeles, Los Angeles, CA, USA; Integrative Center for Addictions, University of California at Los Angeles, Los Angeles, CA, USA FRANCES K. JOHNSON  Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA GEORG JUCKEL  Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr-University, Bochum, Germany ARIE KAFFMAN  Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA NABIL KARNIB  Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon RANA BOU KHALIL  Animal Care Facility, American University of Beirut, Beirut, Lebanon FIRAS H. KOBEISSY  Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon KANTHI KIRAN KONDEPUDI  National Agri-food Biotechnology Institute (NABI), Mohali, Punjab, India JOHN H. KRYSTAL  Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA ASHOK KUMAR  McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA BERNARD LE FOLL  Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Addictions Division, CAMH, Toronto, ON, Canada; Department of Pharmacology and Toxicology, King’s College Circle, University of Toronto, Toronto, ON, Canada BRANDON LEVIN  Department of Psychiatry, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL, USA HANNE LEYSEN  Receptor Biology Lab, Department of Biomedical Research, University of Antwerp, Antwerp, Belgium; Faculty of Pharmacy, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium HE LI  Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA XIAOXIA LI  Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA ZHANJIANG LI  Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Center of Schizophrenia, Beijing Institute for Brain Disorders, Beijing, China ZHISHENG LIU  Department of Pediatric Neurology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China A. S. MACHADO  i3S-Instituto de Investigac¸a˜o e Inovac¸a˜o em Sau´ de, University of Porto, Porto, Portugal; FMUP-Faculty of Medicine, University of Porto, Porto, Portugal; Department of Clinical Neurosciences and Mental Health, Centro Hospitalar UniversitA˜ rio Sa˜o Joa˜o, Porto, Portugal GHADIR MAKKI  Faculty of Sciences, Lebanese University, Beirut, Lebanon JOELLE MAKOUKJI  Neurogenetics Program, Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine, AUBMC Special Kids Clinic, American University of Contributors xxi

Beirut Medical Center, Beirut, Lebanon; Department of Biochemistry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon LINE MANCEAU  Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, UK BRONWEN MARTIN  Faculty of Pharmacy, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium STUART MAUDSLEY  Receptor Biology Lab, Department of Biomedical Research, University of Antwerp, Antwerp, Belgium; Faculty of Pharmacy, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium YASSER MEDLEJ  Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon PATRICIA MESA-GRESA  Department of Psychobiology, University of Valencia, Valencia, Spain ABDELHALEM MESFIOUI  Laboratory of Genetics, Neuroendocrinology, and Biotechnology, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco WAEL MOHAMED  Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Al Minufya, Egypt; Department of Basic Medical Science, Kulliyyah of Medicine, International Islamic University, Kuantan, Pahang, Malaysia STEFANIA MONDELLO  Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy; “Oasi” Institute for Research on Mental Retardation and Brain Aging (I.R.C.C.S.), Troina, EN, Italy SANTIAGO MONLEO´ N  Department of Psychobiology, University of Valencia, Valencia, Spain MANUEL MORRENS  Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Department of Psychiatry, University of Antwerp, Duffel, Belgium WILLIAM H. J. NORTON  Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, UK PAUL NOUFI  Department of Psychiatry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon MAKRAM OBEID  Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Division of Child Neurology, Department of Pediatric and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon CAITLIN A. ORSINI  Department of Psychiatry, University of Florida, Gainesville, FL, USA ALI OUICHOU  Laboratory of Genetics, Neuroendocrinology, and Biotechnology, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco STEVEN PETERSON  Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, Kingsville, TX, USA S. PINTO  i3S-Instituto de Investigac¸a˜o e Inovac¸a˜o em Sau´ de, University of Porto, Porto, Portugal; FMUP-Faculty of Medicine, University of Porto, Porto, Portugal; Department of Clinical Neurosciences and Mental Health, Centro Hospitalar Universita´rio Sa˜o Joa˜o, Porto, Portugal J. PRATA  i3S-Instituto de Investigac¸a˜o e Inovac¸a˜o em Sau´ de, University of Porto, Porto, Portugal; FMUP-Faculty of Medicine, University of Porto, Porto, Portugal; Department of Psychiatry and Mental Health, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal YANJIE QI  Laboratoire de Neuroge´ne´tique, Centre de Recherche, Institut Universitaire en Sante´ Mentale de Montre´al, Montreal, QC, Canada; Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China xxii Contributors

ROSA REDOLAT  Department of Psychobiology, University of Valencia, Valencia, Spain FLORIAN REICHMANN  Otto Loewi Research Centre, Medical University of Graz, Graz, Austria NEIL E. ROWLAND  Department of Psychology, University of Florida, Gainesville, FL, USA SARAH SAAD  Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon HOUSSEIN SALAH  Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon MOHAMED SALAMA  Faculty of Medicine, Medical Experimental Research Center (MERC), Mansoura University, Mansoura, Egypt; Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Atlantic Fellow for Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland S. G. SANTOS  i3S-Instituto de Investigac¸a˜o e Inovac¸a˜o em Sau´ de, University of Porto, Porto, Portugal; INEB-Instituto de Engenharia Biome´dica, University of Porto, Porto, Portugal; ICBAS-Instituto de Cieˆncias Biome´dicas Abel Salazar, University of Porto, Porto, Portugal VALENTINA SATTA  Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy MARIA SCHERMA  Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy BARRY SETLOW  Department of Neuroscience, University of Florida, Gainesville, FL, USA; Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA; Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL, USA ABDULLAH SHAITO  Department of Biological and Chemical Sciences, Faculty of Arts and Sciences, Lebanese International University, Beirut, Lebanon WAEL SHAMSEDDEEN  Department of Psychiatry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA NICHOLAS W. SIMON  Department of Psychology, University of Memphis, Memphis, TN, USA DHIRENDRA PRATAP SINGH  Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Punjab University, Chandigarh, India; National Agri-food Biotechnology Institute (NABI), Mohali, Punjab, India A. BENJAMIN SRIVASTAVA  Division on Substance Use Disorder, Department of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY, USA ALEXANDRA STOLYAROVA  Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA YASMEEN M. TAALAB  Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; German Institute of Disaster Medicine and Emergency Medicine, Tubingen, Germany FARID TALIH  Department of Psychiatry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Psychiatry Department, American University of Beirut Medical Center, Beirut, Lebanon LAHCEN TAMEGART  Neurosciences, Pharmacology and Environment Unit, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh, Morocco SIJIE TAN  Department of Psychiatry, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL, USA YARA TARABAY  Faculty of Pedagogy, Lebanese University, New Rawda, Lebanon; Faculty of Natural and Applied Sciences, Notre Dame University, Louaize, Lebanon Contributors xxiii

HALE Z. TOKLU  Department of Clinical Sciences, University of Central Florida College of Medicine, Gainesville, FL, USA; HCA North Florida Division, Graduate Medical Education, Tallahassee, FL, USA JOSE M. TRIGO  Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada ROBERT J. URSANO  Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA JAANA VAN GASTEL  Receptor Biology Lab, Department of Biomedical Research, University of Antwerp, Antwerp, Belgium; Faculty of Pharmacy, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium LEN VEENKER  Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Antwerp, Belgium CONCEPCIO´ N VINADER-CAEROLS  Department of Psychobiology, University of Valencia, Valencia, Spain O. VON DOELLINGER  i3S-Instituto de Investigac¸a˜o e Inovac¸a˜o em Sau´ de, University of Porto, Porto, Portugal; FMUP-Faculty of Medicine, University of Porto, Porto, Portugal; Department of Psychiatry and Mental Health, Centro Hospitalar do Taˆmega e Sousa, Penafiel, Portugal LARA WADI  Faculty of Medicine, American University of Beirut, Beirut, Lebanon KEVIN K. W. WANG  Department of Emergency Medicine, University of Florida, Gainesville, FL, USA LAN WEI  Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA SARAH WEHBE  Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon JORDON D. WHITE  Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA ISAAC WILKS  Department of Psychiatry, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL, USA LAN XIONG  Laboratoire de Neuroge´ne´tique, Centre de Recherche, Institut Universitaire en Sante´ Mentale de Montre´al, Montreal, QC, Canada; De´partement de Psychiatrie, Faculte´ de Me´decine, Universite´ de Montre´al, Montreal, QC, Canada; Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada ZHIUI YANG  Department of Emergency Medicine, University of Florida, Gainesville, FL, USA BRITTNEY YEGLA  McKnight Brain Institute, University of Florida, Gainesville, FL, USA TIANZHENG YU  Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Department of Military and Emergency Medicine, Consortium for Health and Military Performance, Uniformed Services University of the Health Sciences, Bethesda, MD, USA LEI ZHANG  Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA YI ZHENG  Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Center of Schizophrenia, Beijing Institute for Brain Disorders, Beijing, China