Overview

mSka members seek to identify the molecular basis of severe psychiatric conditions in order to improve the quality of life for effected individuals. We are primarily interested in ameliorating those processes that allow for deleterious motivations and choices to impact societal and familial interactions. Specifically, these phenomena are studied in models of alcoholism, cocaine addiction, methamphetamine addiction, and schizophrenia spectrum disorder. Additionally, mSka findings are being developed into diagonistic tools.

Collaborators

mSka benefits from rich collaboration with several members of the VCU community including: the Alcohol Research Center, Chemical & Life Science Engineering, Human & Molecular Genetics, the Institute of Drug & Alcohol Studies, Medicinal Chemistry, Nanoscience & Nanotechnology, Neurobiology, Pharmacology, Psychiatry, Department of Radiology Center for Molecular Imaging, and the Virginia Institute for Psychiatric and Behavioral Genetics.

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Alcoholism

Alcohol abuse continues to extract significant economic and societal resources. This is due, in part, to an increase in the motivation to seek alcohol that develops over time. This heightened motivation to seek alcohol often continues to manifest as chronic recidivism in individual seeking abstinence. Few pharmacotherapies are available to the clinician and those that are available present either with low compliance or low efficacy. Development of more robust treatment regimens is hampered by pre-clinical models of alcoholism that often fail rigorous validity criteria and/or do not yield desired levels of pharmacological intoxication. Thus, mSka efforts are divided into two major, yet related tracks.

 

First, we seek to develop simple and efficient models of alcoholism with which specific aspects of alcoholism can be probed at the molecular level. Second, we seek to understand the molecular mechanisms through which the etiology of pathological alcohol-seeking develops and is expressed as relapse. Thus, our overall goal is to identify novel regulators of this heightened motivation to seek alcohol and, further, to ameliorate alcoholism by specifically targeting these mechanisms. To date, our efforts along with our collaborators have identified the Activators of G-protein Signaling 3/ G-protein Signaling Modulator 1 and the Small Conductance, Calcium-Activated Potassium Channel, 3rd Subunit as highly promising candidates warranting further investigation.

 

Alcoholism is a multifaceted disease, and as such, it is improbable that a single molecule is solely responsible for the disease. Thus, our search to identify and to correct the molecular basis of alcoholism continues and is supported by the efforts of other members of the VCU Alcohol Research Center, VCU Institute of Drug and Alcohol Studies, Department of Pharmacology, and the Virginia Institute for Behavioral and Psychiatric Genetics.

Diagnostic Tools

Quantitative tools for the accurate diagnosis of severe psychiatric conditions are lacking. This is unlike any other area of modern medicine. For example, precise laboratory and clinical measures are available to assist in the diagnosis of high cholesterol, strep throat, and fractured bones. Unfortunately, psychiatrists and psychologists lack the assistance of these unequivocal diagnostic tools. We are actively working across scientific disciplines in order translate the findings of molecular and systems neuroscientists into diagnostic agents with clear clinical utility.

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Psychostimulant Addiction

The psychostimulants (cocaine and crystal meth) rewire brain circuitry and reshape cell shape and molecular make up. Many of these changes are long-lived even into protracted periods of abstinence. These long-lasting changes are hypothesized to interfere with abstinence efforts. Our goal is to determine if and how these alterations contribute to addiction and relapse. Specifically, we are most interested in determining the molecular basis of the motivation and choice to seek psychostimulants despite mounting deleterious consequences. Importantly, we use this information to design novel interventions that could be efficacious in future clinical interventions.

 

To date our efforts along with our collaborators have identified several promising candidates including the Activators of G-protein signaling 3/ G-protein Signaling Modulator 1, Homer 1a, and the Glial Fibrillary Acidic Protein. Spurred on by these successes, our search continues to identify and correct the molecular basis of psychostimulant addiction. Importantly, these efforts benefit from rich collaborations with other members of the VCU Institute of Drug and Alcohol Studies, Department of Pharmacology, and the Virginia Institute for Behavioral and Psychiatric Genetics.

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Schizophrenia Spectrum Disorder

Among the spectrum of schizophrenia disorders, the symptoms that most limit the quality-of-life and reintegration of affected individuals is deficits in working memory. Working memory is a short term and highly flexible form of memory that is utilized to solve common tasks on a daily basis. Efficient working memory is most important when in the midst of continually changing variables. For example, recalling that the car was parked on another block due to street sweeping is one example of working memory. Another might be re-evaluating the most efficient combination of bus and cab required to keep an appointment given that the initially planned bus was just missed. A neurobiological phenomena known as hypofrontality is thought to underly many of the working memory deficits that are observed in schizophrenia spectrum disorder.

 

We have just began our efforts at understanding and correcting the molecular basis of working memory deficits in models of hypofrontality and this remains an active area of research that is supported through collaborations with other investigators in the Virginia Institute for Psychiatric & Behavioral Genetics.

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