ADDICTIONS – FROM PATHOPHYSIOLOGY TO TREATMENT Edited by David Belin Addictions – From Pathophysiology to Treatment Edited by David Belin Contributors Aude Belin-Rauscent, David Belin, José Vicente Negrete-Díaz, Gonzalo Flores, Talvinder S. Sihra, Antonio Rodríguez-Moreno, Edgar Antonio Reyes-Montaño, Edwin Alfredo Reyes-Guzmán, Ezio Carboni, Roberto Cadeddu, Anna Rosa Carta, Sonia Luz Albarracín Cordero, Bernd Robert Stab II, Felipe Guillen, Edgar Antonio Reyes Montano, Alfredo Ramos-Miguel, María Álvaro-Bartolomé, M. Julia García-Fuster, Jesús A. García-Sevilla, Marta Rodríguez-Arias, María Asunción Aguilar, Karen M. von Deneen, Yijun Liu, M.L. Laorden, M. V. Milanés, P. Almela, Zheng-Xiong Xi, Jennifer E. Murray, Jérôme Lacoste, David Belin, Cynara Teixeira Ribeiro, Andréa Hortélio Fernandes, Andrea Leonardi, Sonia Scavelli, Gianluca Ciuffardi, Paolo Stocco, Alessandra Simonelli, Nicoletta Capra, Francesca De Palo, Philippe Chossegros Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Masa Vidovic Typesetting InTech Prepress, Novi Sad Cover InTech Design Team First published October, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Addictions – From Pathophysiology to Treatment, Edited by David Belin p. cm. ISBN 978-953-51-0783-5 Contents Preface IX Section 1 General Considerations 1 Chapter 1 Drug Addictions: An Historical and Ethological Overview 3 Aude Belin-Rauscent and David Belin Chapter 2 Animal Models of Drug Addiction 21 Aude Belin-Rauscent and David Belin Section 2 Pathophysiology of Addictions 65 Chapter 3 Addictive Drugs and Synaptic Plasticity 67 José Vicente Negrete-Díaz, Gonzalo Flores, Talvinder S. Sihra and Antonio Rodríguez-Moreno Chapter 4 Cocaine Addiction: Changes in Excitatory and Inhibitory Neurotransmission 103 Edgar Antonio Reyes-Montaño and Edwin Alfredo Reyes-Guzmán Chapter 5 Role of Prefrontal Cortex Dopamine and Noradrenaline Circuitry in Addiction 129 Ezio Carboni, Roberto Cadeddu and Anna Rosa Carta Chapter 6 A Molecular Mechanism of Ethanol Dependence: The Influence of the Ionotropic Glutamate Receptor Activated by N-Methyl-D-Aspartate 169 Sonia Luz Albarracín Cordero, Bernd Robert Stab II, Felipe Guillen and Edgar Antonio Reyes Montano Chapter 7 Role of Multifunctional FADD (Fas-Associated Death Domain) Adaptor in Drug Addiction 201 Alfredo Ramos-Miguel, María Álvaro-Bartolomé, M. Julia García-Fuster and Jesús A. García-Sevilla Chapter 8 Polydrug Use in Adolescence 227 Marta Rodríguez-Arias and María Asunción Aguilar VI Contents Chapter 9 Food Addiction, Obesity and Neuroimaging 259 Karen M. von Deneen and Yijun Liu Chapter 10 Pathways Involved in the Cardiac Adaptive Changes Observed During Morphine Withdrawal 291 M.L. Laorden, M. V. Milanés and P. Almela Section 3 Addiction Treatment – Pharmacology 309 Chapter 11 Medication Development for the Treatment of Cocaine Addiction – Progress at Preclinical and Clinical Levels 311 Zheng-Xiong Xi Chapter 12 N-Acetylcysteine as a Treatment for Addiction 355 Jennifer E. Murray, Jérôme Lacoste and David Belin Section 4 Therapeutic Strategies – Behavioural, Social and Analytical Approaches 381 Chapter 13 Proposals for the Treatment of Users of Alcohol and Other Drugs: A Psychoanalytic Reading 383 Cynara Teixeira Ribeiro and Andréa Hortélio Fernandes Chapter 14 The Interactional Approach in the Treatment of Cocaine Addicts 403 Andrea Leonardi, Sonia Scavelli and Gianluca Ciuffardi Chapter 15 Research and Intervention for Drug-Addicted Mothers and Their Children: New Perspectives 425 Paolo Stocco, Alessandra Simonelli, Nicoletta Capra and Francesca De Palo Chapter 16 HCV and Drug Use – What Can Be Learned from the Failure to Control This Epidemic? 453 Philippe Chossegros Preface Addiction is the psychiatric disorder for which the definition has evolved the most in the last thirty years. From the DSM-III in which addiction was defined as tolerance and withdrawal to the current clinical definition in the DSM-IV and upcoming DSM- V, with five out of seven criteria referring to loss of control over, and compulsive use of, drugs, the social and medical views of addictions have dramatically changed. Drug addiction is no longer a question of altered “psychophysical need” of the drug. It is beyond this, an alteration of both the basic, i.e., reward, and sophisticated systems of the brain, including attention, behavioural control, decision making, memory, and even insight. Despite this updated neurological understanding, drug addicts remain considered by the general public as mere criminals with very weak willpower. This general wisdom must change especially in the face of the current trends towards increasing recreational use of drugs worldwide, and the emergence of the easy access to online casinos and gaming Indeed, most of us, if not all, have already been exposed to a stimulus with addictive properties, thereby having gambled with a potential fall into the vicious cycle that is addiction. As such, it is important to keep in mind that tobacco and alcohol, including wine, are among the most dangerous addictive drugs, causing the majority of drug-related deaths. Behind the legal status of drugs and the relative failure in law enforcement management, remains our lack of understanding of the psychological, neurobiological, and environmental factors that contribute to the transition from controlled recreational drug use to compulsive drug use. In other words, to date, we still do not know why some people exposed to addictive stimuli will develop an addiction while others will be able to use these drugs recreationally throughout their life without succumbing to the negative personal, societal, and legal side effects of drug consumption. Hence, we have no effective prevention strategies nor do we have effective individual-based therapeutic treatments to offer. In the search for an effective treatment, as a psychobiologist, I suggest that addiction is a loss of prefrontal executive control over a maladaptive incentive habit process that bridges limbic pavlovian impulses originating from the amygdala and the insula to a X Preface rigid habit system dependent upon the dorsolateral striatum. We therefore must find a way to counteract this between-systems adaptation, with the most promising approach being pharmacological tools. However, this psychobiolgical model does not capture key aspects of the pathology, such as the economic status of the addict, his current social and personal environment, the unique history that drove him to the use of a particular drug, whether his addiction involves the use of several different drug classes and so on. Since the now well-accepted claim that addiction is a brain disease has opened the potential development of pharmacological treatment based on a better understanding of addiction pathophysiology, many researchers have focused on the understanding of the neurobiological adaptations to drug exposure. They have forgotten that the neurobiological adaptations to exposure to addictive drugs are common to all that are exposed to drugs, whether they be addicted or not. It is only recently that the interest in inter-individual vulnerability to compulsive drug use has emerged in the field of neuroscience, and the additional potential role of environmental conditions is only emerging. Several outstanding books have now been published covering the neurobiology of drug addiction and aiming to provide a rather exhaustive overview of the current state of addiction research integrating these issues. Here, we offer an alternative point of view focusing on the complexity and heterogeneity of treatment management of addictions involving players from the legal, medical, social, psychological, neurobiological, psychiatric, and psychoanalytical fields. None of these fields and associated management strategies has so far proven to have developed effective treatment to prevent relapse of compulsive drug use in drug addicts. This lack of success may stem from the fact that there are several forms of addiction with specific etiologies and pathophysiologies that we have no insights into, but it may also be explained by a lack of interaction and understanding among the different approaches involved in the management of addiction. Indeed, not only a brain disease, addiction should be additionally considered in terms of comorbidity, both at the psychiatric and somatic levels. By emphasizing how much the definition of addiction and the foreseen potential treatments differ among biologists, psychologists, psychoanalysts, or GPs, this book provides an original framework whereby one can reach beyond an initial area of interest regarding addictions. This book also provides insights into the experimental approaches of drug addiction, both in preclinical models and in humans, as well as the neurobiological mechanisms that may be associated with addictions. It provides a synthesis of the current and emerging pharmacological tools for the management of addiction to different drugs and opens new perspectives on various management strategies of drug addicts. Gathering experts in different fields, from basic research to the clinic, involved in the . ADDICTIONS – FROM PATHOPHYSIOLOGY TO TREATMENT Edited by David Belin Addictions – From Pathophysiology to Treatment Edited by David. be obtained from orders@intechopen.com Addictions – From Pathophysiology to Treatment, Edited by David Belin p. cm. ISBN 978-953-51-0783-5