The Role Of Serotonin And Vesicular Monoamine Transporters In The Adverse Responses To Methylenedioxymethamphetamine


Book Description

3,4-(±)-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a widely abused amphetamine derivative with potent stimulant properties. The neuropharmacological effects of MDMA are biphasic in nature. MDMA initially causes synaptic monoamine release, primarily of serotonin (5-HT), producing hyperthermia and hyperactivity (5-HT syndrome). Conversely, the long-term effects of MDMA manifest as a prolonged depletion in 5-HT, and structural damage to serotonergic nerve terminals. Monoamine transporter systems at the plasma membrane and storage vesicles of 5-HT neurons have been implicated in MDMA toxicity. Nonetheless, many mechanistic questions remain regarding the precise role of uptake transporters in MDMA neurotoxicity. The present study was designed to address the importance of the serotonin reuptake transporter (SERT) and the vesicular monoamine transporter 2 (VMAT2) to the physiological, behavioral and neurotoxic responses to MDMA. SERT functions as a primary regulator of 5-HT homeostasis, mediating the reuptake of 5-HT from the synaptic space following its release during neurotransmission. SERT is a molecular target site for MDMA and many antidepressant agents such as the selective serotonin reuptake inhibitor (SSRI) class. Pharmacological inhibition of SERT protects against MDMA-induced serotonergic neurotoxicity. Thus, the effects of MDMA are in part mediated by an ability to interact with and inhibit SERT. Using a SERT-knockout (SERT-KO) rat model, we determined that SERT deficiency modulated the acute toxicities of MDMA, such as hyperthermia and hyperactivity, whilst completely preventing long-term depletions in tissue 5-HT levels, indicating the abolishment of neurotoxicity. Disruption of vesicular monoamine storage via interaction with VMAT2 has also been implicated in MDMA neurotoxicity. VMAT2 participates in the transport of monoamine neurotransmitters, in particular 5-HT and dopamine (DA), into intra-neuronal storage vesicles. As such, VMAT2 is critical in maintaining neuronal health by preventing neurotransmitter oxidation within the cytosol. Pharmacological inhibition of VMAT2 with Ro4-1284 reduced MDMA-induced hyperactivity and averted hyperthermia along with persistent serotonergic deficits. Overall, our results corroborate the hypothesis that SERT and VMAT2 are critical to the in vivo effects of MDMA. Furthermore, given that VMAT2 inhibition diminished the behavioral response to MDMA in rats, pharmacological manipulation of this transporter could be used in the treatment of MDMA abuse and overdose.




Imaging in Parkinson's Disease


Book Description

Imaging in Parkinson's Disease provides up-to-date information concerning new applications of brain imaging to the study of Parkinson's disease. Written by experts in the field, the book focuses on structural and functional imaging methodologies that have recently been applied to study the natural history of Parkinson's disease, with emphasis on the development of the major motor manifestations of the illness as well as cognitive impairment and dementia.




The Effects of Drug Abuse on the Human Nervous System


Book Description

Drug use and abuse continues to thrive in contemporary society worldwide and the instance and damage caused by addiction increases along with availability. The Effects of Drug Abuse on the Human Nervous System presents objective, state-of-the-art information on the impact of drug abuse on the human nervous system, with each chapter offering a specific focus on nicotine, alcohol, marijuana, cocaine, methamphetamine, MDMA, sedative-hypnotics, and designer drugs. Other chapters provide a context for drug use, with overviews of use and consequences, epidemiology and risk factors, genetics of use and treatment success, and strategies to screen populations and provide appropriate interventions. The book offers meaningful, relevant and timely information for scientists, health-care professionals and treatment providers. - A comprehensive reference on the effects of drug addiction on the human nervous system - Focuses on core drug addiction issues from nicotine, cocaine, methamphetamine, alcohol, and other commonly abused drugs - Includes foundational science chapters on the biology of addiction - Details challenges in diagnosis and treatment options




Movement Disorders


Book Description

The use of animal models is a key aspect of scientific research in numerous fields of medicine. This book vigorously examines the important contributions and application of animal models to the understanding of human movement disorders and will serve as an essential resource for basic neuroscientists engaged in movement disorders research. Academic clinicians, translational researchers and basic scientists are brought together to connect experimental findings made in different animal models to the clinical features, pathophysiology and treatment of human movement disorders. A vital feature of this book is an accompanying DVD with video clips of human movement disorders and their corresponding animal models. The book is divided into sections on Parkinson disease, Huntington disease, dystonia, tremor, paroxysmal movement disorders, ataxia, myoclonus, restless legs syndrome, drug-induced movement disorders, multiple system atrophy, progressive supranuclear palsy/corticobasal degeneration and spasticity. This book serves as an essential resource for both clinicians interested in the science being generated with animal models and basic scientists studying the pathogenesis of particular movement disorders.* Provides a single comprehensive resource on animal models of movement disorders that academic clinicians, translational researchers, and basic neuroscientists can refer to* Includes contributions by expert movement disorder clinicians and top-level researchers in the field* Features a DVD containing over 170 video clips of human movement disorders and the corresponding animal models




A New Era of Catecholamines in the Laboratory and Clinic


Book Description

This new volume of Advances in Pharmacology presents catecholamine symposium proceedings. Chapters cover such topics as cellular dynamics of catecholamine release and re-uptake, catecholamines in mood regulation and imaging catecholamine transporters. With a variety of chapters and the best authors in the field, the volume is an essential resource for pharmacologists, immunologists and biochemists alike. - Presents catecholamine symposium proceedings - Chapters cover a variety of topics such as cellular dynamics of catecholamine release and re-uptake, catecholamines in mood regulation and imaging catecholamine transporters - With the best authors in the field, the volume is an essential resource for pharmacologists, immunologists and biochemists alike




Imaging of the Human Brain in Health and Disease


Book Description

Brain imaging technology remains at the forefront of advances in both our understanding of the brain and our ability to diagnose and treat brain disease and disorders. Imaging of the Human Brain in Health and Disease examines the localization of neurotransmitter receptors in the nervous system of normal, healthy humans and compares that with humans who are suffering from various neurologic diseases. Opening chapters introduce the basic science of imaging neurotransmitters, including sigma, acetylcholine, opioid, and dopamine receptors. Imaging the healthy and diseased brain includes brain imaging of anger, pain, autism, the release of dopamine, the impact of cannabinoids, and Alzheimer's disease. This book is a valuable companion to a wide range of scholars, students, and researchers in neuroscience, clinical neurology, and psychiatry, and provides a detailed introduction to the application of advanced imaging to the treatment of brain disorders and disease. - A focused introduction to imaging healthy and diseased brains - Focuses on the primary neurotransmitter release - Includes sigma, acetylcholine, opioid, and dopamine receptors - Presents the imaging of healthy and diseased brains via anger, pain, autism, and Alzheimer's disease




Network Neuroscience


Book Description

Studying brain networks has become a truly interdisciplinary endeavor, attracting students and seasoned researchers alike from a wide variety of academic backgrounds. What has been lacking is an introductory textbook that brings together the different fields and provides a gentle introduction to the major concepts and findings in the emerging field of network neuroscience. Network Neuroscience is a one-stop-shop that is of equal use to the neurobiologist, who is interested in understanding the quantitative methods employed in network neuroscience, and to the physicist or engineer, who is interested in neuroscience applications of mathematical and engineering tools. The book spans 27 chapters that cover everything from individual cells all the way to complex network disorders such as depression and autism spectrum disorders. An additional 12 toolboxes provide the necessary background for making network neuroscience accessible independent of the reader's background. Dr. Flavio Frohlich wrote this book based on his experience of mentoring dozens of trainees in the Frohlich Lab, from undergraduate students to senior researchers. The Frohlich lab pursues a unique and integrated vision that combines computer simulations, animal model studies, human studies, and clinical trials with the goal of developing novel brain stimulation treatments for psychiatric disorders. The book is based on a course he teaches at UNC that has attracted trainees from many different departments, including neuroscience, biomedical engineering, psychology, cell biology, physiology, neurology, and psychiatry. Dr. Frohlich has consistently received rave reviews for his teaching. With this book he hopes to make his integrated view of neuroscience available to trainees and researchers on a global scale. His goal is to make the book the training manual for the next generation of (network) neuroscientists, who will be fusing biology, engineering, and medicine to unravel the big questions about the brain and to revolutionize psychiatry and neurology. - Easy-to-read, comprehensive introduction to the emerging field of network neuroscience - Includes 27 chapters packed with information on topics from single neurons to complex network disorders such as depression and autism - Features 12 toolboxes serve as primers to provide essential background knowledge in the fields of biology, mathematics, engineering, and physics




Synthetic Cathinones


Book Description

Over the last decade, and particularly during the recent five years, a rapidly increasing number of novel psychoactive substance (NPSs), often marketed as “designer drugs”, “legal highs”, “herbal highs”, “research or intermediate chemicals” and “laboratory reagents”, has appeared on the drug market in an effort to bypass controlled substance legislation. NPSs encompass a wide range of different compounds and drug classes but had been dominated by synthetic cannabinomimetics and psychostimulatory synthetic cathinones, so-called β-keto amphetamines. Compounds from the later class were first detected in Europe in 2004, and since then 103 new cathinones have been identified and reported to the European Monitoring Centre for Drugs and Drug Addiction, with 57 during the last two years. Synthetic cathinones – novel addictive and stimulatory psychoactive substances is the first publication of this kind that provides readers with background on chemical structures, detection, prevalence and motivation of use of the very popular group of NPSs. This book also presents comprehensive overview of the mechanisms of action, pharmacological activity, and main metabolic pathways of synthetic cathinones, followed by a detailed discussion of the acute and chronic toxicity associated with the use of these substances. Written by international experts in the field, this multi-authored book is a valuable reference not only for scientists, clinicians and academics, but also for readers representing different professional background who are involved in educational-prophylactic activities directed to harm reduction of psychoactive compounds.




Brain Mapping


Book Description

Brain Mapping: The Disorders is the first comprehensive text to describe the uses of the latest brain mapping technologies in the evaluation of patients with neurological, neurosurgical and psychiatric disorders. With contributions from the leading figures in the field, this heavily illustrated text is organized by disorders of brain systems, with specific examples of how one should use current neuroimaging techniques to evaluate patients with specific cerebral disorders. Comprehensive in scope, the text discusses patient evaluations using the wide range of modern magnetic resonance imaging techniques, positron emission tomography, single photon emission computed tomography, optical intrinsic signal imaging, electroencephalography, magnetoencephalography, and transcranial magnetic stimulation. The third in this brain mapping series, Brain Mapping: The Disorders, is the ultimate text for anyone interested in the use of brain mapping techniques to study patients with disorders of the central nervous system. Provides a comprehensive, in-depth view of the current brain mapping techniques as they are used in the evaluation of patients with cerebral disorders Heavily illustrated to provide actual examples of the use of the specific techniques Includes contributions from the leaders in the field ensure authoritative and up-to-date material Completes the trilogy of three brain mapping texts dealing, respectively, with the methods, the applications of these methods in the normal brain and in patients with neurological, neurosurgical, and psychiatric disorders




Drug Induced Movement Disorders


Book Description

The second revised edition of this text will update and present current state of the art clinical approaches to this subject. This book will continue to be the source text of information on drug-induced movement disorders authored and edited by the pioneers in the field. It will be an invaluable addition to the library of any neurologist.