George F. Koob, Ph.D.
* On leave of absence to direct the National Institute on Alcohol Abuse and Alcoholism.
The faculty of the Committee on the Neurobiology of Addictive Disorders is comprised of a group of ten investigators with a common goal of understanding the function of the brain emotional systems and to understand how these systems malfunction in disease. The research programs in the Committee on the Neurobiology of Addictive Disorders are focused on the neurobiological mechanisms involved in motivated and emotional behavior and how these mechanisms are altered with the development of central nervous system pathology such as addiction, stress, and eating disorders. The research domains of the faculty of the Committee integrate and translate basic research findings across multiple domains from cell biology to neurocircuitry to clinical. The Committee also forms the foundation for the Pearson Center for Alcoholism and Addiction Research with the goal of developing novel medications for the treatment of addictive disorders. Detailed results of Committee activity in clinical, neuropsychology, neuropharmacology, neurochemistry, neurophysiology and neuroendocrinology domains are covered in the reports of B. Mason, M. Taffe, G. Koob, L. Parsons, E. Zorrilla, and M. Roberto. Here, I summarize what our faculty are doing and the background that led to this work.
Barbara Mason, Ph.D., Professor**
** Acting Chair
Dr. Mason has been a leader in the field of development of treatment of psychiatric disorders including depression and addiction. Currently, her work is focused on the clinical evaluation of medications for the treatment of substance dependence. Ongoing studies have the aim of development of medications that reduce the risk of relapse, and the signs and symptoms of protracted abstinence. Her approach involves short-term human laboratory studies as well as long-term double-blind placebo controlled clinical trials. Her current NIH-funded work focuses on the development of new Pharmacological treatents for alcohol and cannabis dependence. Dr. Mason is Co-Director of the Pearson Center for Alcoholism and Addiction Research and is a current Merit awardee from the National Institute on Alcohol Abuse and Alcoholism.
Loren (Larry) Parsons, Ph.D., Professor
Dr. Parsons has a long-term interest in the neurochemical/neuropharmacological changes that occur in critical brain motivational circuits associated with reward disregulation in addiction. His current work is focused on the exciting area of how self-administration of drugs of abuse affect endogenous endocannabinoids in the brain. Dr. Parsons and his team have identified specific endocannabinoid effects in specific brain areas linked to specific components of the drug dependence cycle: drug reward, withdrawal and reinstatement of drug seeking. Alcohol withdrawal is associated with decreases in endocannabinoid activities in the central nucleus of the amygdala providing a potential key component of neuroadaptation associated with alcohol dependence.
Michael Taffe, Ph.D., Associate Professor
Dr. Taffe has a major interest in the physiological, motivational and cognitive sequelae resulting from use and abuse of drugs of abuse. Using a primate model, the rhesus macaque, he has discovered that 3, 4-methylenedioxymethamphetamine (MDMA, also known as "Ecstasy") and associated amphetamine drugs produce profound hyperthermia that is not a direct result of increases in activity produced by these drugs. Dr. Taffe directs the primate neurobehavioral laboratory and current work is engaged in bridging our cellular neurobiological studies in the rodent work to the human clinical situation.
Eric Zorrilla, Ph.D., Associate Professor
Dr. Zorrilla has a focus of his work on how the brain reward and stress systems control food intake an area of great current relevance because of the high incidence of obesity in the United States and the resulting secondary health consequences. Dr. Zorrilla and his team in collaboration with Dr. Janda (Department of Chemistry), have identified a key player in the control of appetite, ghrelin, that is produced by the stomach and signals to the brain a requirement for energy. Immunization of antibodies against ghrelin slowed the accumulation of body weight and rat in rats. In addition, Dr. Zorrilla and his team have begun to characterize a pattern of binge-like palatable food intake that generates a physiological profile not unlike some aspects of addictive-like behavior and the neurobiological basis for this phenomenon is being explored.
Marisa Roberto, Ph.D., Associate Professor
Dr. Roberto is exploring the effects of drugs of abuse on the cellular physiology of the central nucleus of the amygdala, a key structure in the brain involved in emotional processing. Using cellular recording of neuronal activity in slices of the amygdala, Dr. Roberto and her team have identified key changes in the activity of both GABAergic and glutamatergic neurons with acute and chronic alcohol. Even more exciting is that the alcohol effects on activity of these neurons appear to be mediated by actions on neuropeptides such as corticotropin releasing factor and nociceptin that have been shown neuropharmacologically to have a key role in mediating neuroadaptation to the actions of alcohol. These studies provide a key translation of the neurocircuitry and neuropharmacological studies of the Committee to the level of cellular interactions. Dr. Roberto won the Young Investigator Award from the Research on Alcoholism in 2006
Chitra Mandyam, Ph.D., Associate Professor
Dr. Mandyam has been recruited to the Committee on as an Assistant Professor. She is a cell biologist/neuroscientist who will pursue studies on how stress and drugs of abuse alter the neuroplasticity of the adult brain by examining changes in the birth, survival and dynamics of adult generated neurons. Dr. Mandyam will use techniques including immunohistochemistry, immunoblotting and in situ hybridization to answer specific questions regarding neuroadaptations produced by stress and drugs of abuse that can lead to psychiatric disorders and brain pathology. She has won a career development award for 5 years from the National Institute on Drug Abuse that will support her program.
Candice Contet, Ph.D., Assistant Professor
Dr. Contet investigates the genetic determinants and molecular mechanisms driving excessive alcohol drinking, using mouse models of differential ethanol intake in combination with a variety of genetic tools. A first aspect of her research focuses on known molecular targets of ethanol, such as GIRK and BK channels, and aims to assess the in vivo relevance of ethanol's action on these proteins by evaluating their contribution to intoxication, tolerance, drinking and dependence. A second aspect of her research explores the neurocircuitry mediating the well-established role of extrahypothalamic CRF in the transition to ethanol dependence and in the symptomatology of ethanol withdrawal. Finally, she is undertaking exploratory projects, which aim to identify novel genes contributing to or protecting from excessive drinking. She has recently established mouse models of intravenous cocaine and heroin self-administration and anticipates extending the same approaches used for alcohol to uncover common and distinct determinants of addiction to these substances.
Olivier George, Ph.D., Assistant Professor
Dr. George has major interest in the brain stress and cognitive systems in drug addiction. The main goals of his lab are to unveil the neurobiological mechanisms underlying the transition to drug addiction, and to develop novel pharmacological and non-pharmacological treatments to reduce compulsive drug seeking and taking. Dr George and his team have identified that activation of the CRF system in the extended amygdala and prefrontal cortex during withdrawal mediates excessive nicotine and alcohol intake. He has also demonstrated that escalation of cocaine, methamphetamine and alcohol intake produces a dysfunction of the prefrontal cortex leading to cognitive impairment. Dr. George has also pioneered the development of two novel animal models of escalation of nicotine intake and exposure to electronic cigarette. Current studies are exploring the role of the CRF, dynorphin, hypocretin and steroid systems in addiction to alcohol, nicotine, cocaine and prescription opiates. Dr. George is also CoDirector of the Animal Models/Biochemical Core of the TSRI-Alcohol Research Center and his work is funded by NIAAA and NIDA.
Paul Scweitzer, Ph.D., Associate Professor of Neurobiology of Addictive Disorders
Research in our laboratory focuses on the cellular and molecular mechanisms of action of substances of abuse and their interaction with endogenous transmitter systems in the brain. Our work is centered on cannabinoids and the modulatory role of neuropeptides. To uncover the cellular actions and molecular effectors implicated, we perform electrophysiological recordings from neurons in various brain regions including the hippocampus, the neocortex and the amygdala. Our physiological approach focuses on the modulation of synaptic transmission, synaptic plasticity and ion channels.