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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
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Copyright © 2012 InTech
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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
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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
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