MARC SCIENTISTS
Center Director
Focus: molecular pharmacology of drug addiction and psychiatric disorders
Dr. Janowsky has created a unique environment for exchange between basic and clinical scientists under the MARC,
where discoveries in animal research can be applied to development of human therapy and discoveries from work
in the clinics can be explored with more rigor in the controlled animal models.
Dr. Janowsky's own work focuses on how drugs of abuse impact the release and recycling of dopamine,
a neurotransmitter that is the key neurochemical signaling reward in the brain. Drugs like methamphetamine
disrupt the normal pattern of dopamine's release, leading to the addictive behavior of seeking more drugs.
Drugs of abuse, and especially methamphetamine, are a major concern for Veterans'
Administration hospitals because many veterans who exhibit post-traumatic stress syndrome also have drug addictions.
Scientific Director
Focus: Genetic and neurochemical investigations of risk factors for methamphetamine and alcohol addiction.
Our genetic studies have the potential to identify mechanisms that influence behaviors associated with drug-seeking
as well as behaviors that reflect changes (adaptations) in the brain due to chronic drug use. Our ultimate goal is to identify
pharmacological interventions to treat and prevent addiction. In addition, our genetic research might allow clinicians in
the future to provide genetic counseling to high-risk individuals. We have as a key goal the transfer of information between
non-human and human species to provide the most rigorous analyses.
Administrator
Ruth Rowland, M.A.
Contact for information on Center activities: rowlanru@ohsu.edu.
Scientists
Focus: Functional properties of suprachiasmic nucleus (SCN) neurons, circadian clock regulation, drugs of abuse and non-photic entrainment
The long-term goal of our research is to understand the functional properties of SCN neurons and how the circadian clock regulates these properties. To reach this goal we are pursuing four lines of research: cellular electrophysiology of the suprachiasmatic nucleus;
regulation of retinal input to the SCN;
role of intracellular Ca2+ as a signaling molecule in the circadian system; and characterization of the retinal ganglion cells projecting to the SCN.
Focus: Genetics of sensitivity to drugs of abuse
The Belknap lab uses a wide range of genetic mouse models including inbred strains, intercrosses, selectively-bred lines, knockouts, congenics and ENU mutagen screens to study the genetics of sensitivity to drugs of abuse. One goal is to detect and map to specific chromosomal regions the genes (polygenes) influencing these traits; another goal is to determine the multiple drugs influenced by these quantitative trait loci and how they interact with other genes (gene-gene interactions) throughout the genome.
Focus: Development and use of genetic mouse models to study sensitivity to drugs of abuse.
Dr. Crabbe directs the Animal Core in its efforts to breed mice that are sensitive or resistant
to specific effects of methamphetamine. MARC investigators in the research components then will be able
to use these specific mouse models to map genes affecting impulsivity and methamphetamine's rewarding effects.
Focus: Behavioral assessment of the rewarding and aversive effects of abused drugs.
Dr. Cunningham's lab uses rodent models (rats and mice) to examine the genetic mechanisms, brain systems
and behavioral determinants of drug-seeking, drug-taking and relapse.
Focus: Behavioral processes underlying self-administration, reinforcement, reinstatement, and discrimination of abused drugs in rodents.
During his initial year of MARC pilot funding, Dr. Ford investigated the feasibility of using muscarinic and nicotinic receptor compounds to interfere with the discriminative stimulus effects of methamphetamine (MA) in mice. Promising compounds identified in this earlier work are now being further explored within an oral MA self-administration procedure during a second year of pilot funding. By exploring a combination of MA consumption and discrimination procedures, the involvement of M1 and a4ß2-containing receptor mechanisms in the propensity to seek and consume MA can be assessed, and subsequently manipulated to provide more effective treatment options for MA abusers.
 David Grandy, Ph.D.
Focus: structure, function and expression of G protein-coupled receptors (GPCRs)
Our current efforts are focused on receptors activated by either dopamine or opiates.
Dopamine's effects are mediated by a family of receptors encoded by five genes. We are using molecular and genetic techniques, including the generation of transgenic animals, in an effort to understand the roles that each of these receptors play in a variety of behaviors.
David Hinrichs, Ph.D.
Autoimmune diseases are caused by an immune response to cells or organs of the body. We are developing reagents that specifically modify the immune response against the CNS as occurs in Multiple Sclerosis. Using a mouse model of this disease, we have developed peptide reagents that can block the onset of this experimentally induced disease and can also prevent the relapsing phase of this disease as it develops in this animal model. Presently, we are developing additional reagents to modify the course of disease and prevent its relapsing stage as well as to understand the effectiveness of the immunoregulation that is established.
Focus: Behavioral genetics, drug abuse, neuroimaging, psychopharmacology
The goal of our research is to understand how genes regulate complex behaviors, particularly complex drug-induced behaviors. The behaviors of interest include the stimulant response to ethanol, haloperidol-induced catalepsy, exploratory behavior, acoustic startle and prepulse inhibition. The genetic dimensions of these behaviors can be studied in laboratory animals (generally mice) using classical genetic techniques such as selective breeding and recombinant inbred strategies. Molecular genetic strategies can then be used to map the relevant gene loci and eventually isolate the relevant genes.
Focus: Effects of methamphetamine on cognition and decision-making
Dr. Hoffman's research group studies recovery from the effects of methamphetamine on decision-making using functional MRI.
Better understanding of the time-course of changes in brain function during early abstinence from methamphetamine will help clinicians individualize treatment
and improve chances for success.
Focus: Neuroimmunological mechanisms contributing to cognitive, psychiatric, and substance use disorders
Dr. Huckans' translational research program integrates human, animal, and in vitro experiments to examine how neuroimmune factors contribute to the neuropsychiatric effects of medical, psychiatric, and substance use disorders. Currently, she has VA and NIH funded projects that utilize neuropsychological assessment, neuroimaging, and immunological techniques to study the cognitive and psychiatric effects of methamphetamine dependence, hepatitis C, and traumatic brain injury.
Focus: Associative learning theory; neurobiological basis of learning and memory
My research examines basic learning processes at associative and neurobiological levels of analysis. I am particularly interested in the mechanisms that occur during initial acquisition, in which new relations are established between previously unrelated events, and extinction, which occurs as those relations established during acquisition are severed.
Focus: Neuroimmunological mechanisms contributing to substance abuse, cognitive impairment and depression
Dr. Loftis’s translational research program uses rodents and humans to characterize the inflammatory pathways contributing to cognitive dysfunction and depressogenesis, particularly in patients with a history of substance abuse and hepatitis C. It is hypothesized that circulating inflammatory cytokines act on central nervous system (CNS) cytokine receptors, which in turn stimulate the production of inflammatory mediators (e.g., other proinflammatory cytokines and nitric oxide) in specific brain regions, thus contributing to cognitive impairments and alterations in mood.
Focus: Public-health aspects of substance-abuse research
Through collaboration with colleagues at OHSU, policy makers in state and local government, and practitioners in community treatment programs, Dr. McCarty seeks to increase support for the treatment of alcohol and drug abuse, improve the quality of treatment services, and link policy, practice and research.
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Focus: Epidemiology, biostatistics related to mental health services
Dr. McFarland directs a program of health-services research addressing the impact of managed care on delivery of behavioral health treatments and outcomes. His research encompasses the pharmacoeconomics and pharmacoepidemiology of psychotropic medications.
Focus: Relationship between drug use and both impulsive behavior and risk-taking
Dr. Mitchell's lab uses human and nonhuman subjects to examine whether impulsive
decision-making and risk-taking precedes initiation of drug use, whether neuroadaptations
to drug use impact the propensity to behave impulsively, and whether levels of impulsivity
interact with the ability of individuals to cease drug use.
Focus: Characterization of dopamine receptors
We study how drugs used to treat Parkinson's disease and schizophrenia
bind to dopamine receptors, and what the functional consequences of that
binding are, using cultured cells, neurons, and rat brain tissue.
Focus: Effects of genetic and environmental factors on brain function in mouse models of
neurological diseases.
Using experimental mouse models of human neurological diseases, we analyze brain function,
dissect mechanisms underlying cognitive impairments, and develop tests and treatment strategies
to improve brain function in humans suffering from these diseases. Routinely, we use a
combination of behavioral, neuroendocrinological, pharmacological, neurochemical,
immunohistochemical, cellular, and molecular approaches.
Dr. Rieckmann's work focuses on the implementation, adaptation and clinical evaluation of evidence-based practice in substance abuse treatment. It includes an emphasis on diverse populations, translational research and improving the quality of care through increased access, effectiveness, retention and systems-wide change designed to improve services.
Focus: Neural substrates and molecular mechanisms of drugs of abuse
Dr. Ryabinin's MARC pilot project investigates the role of the corticotropin releasing factor (CRF) peptide system in methamphetamine sensitization and addiction. He also collaborates on Gregory Mark's component using rodent models to identify
brain regions that change activity after self-administration of methamphetamine.
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