Drugs of Abuse Research
The Department of Pharmacology in collaboration with the former Alcohol Research Center (ARC) is in a unique research position because its long history of achievement in classical genetics (development of selected lines and inbred strains of mice) is now proving critical to new molecular genetic approaches. In particular, lines of mice selected for differences in the acute actions of ethanol (Long and Short Sleep) and for differential development of acute tolerance (High and Low Acute Functional Tolerance) provide an opportunity to define the genes that are responsible for these different actions of ethanol. Pharmacology faculty have used the Quantitative Trait Loci (QTL) method to delineate chromosomal regions that contain these genes. Soon, these regions will be narrowed to allow the serious gene "hunting" that will, it is hoped, lead to the first identification of genes responsible for alcohol action. Once identified, the role of these genes in human alcoholism can be determined. Several strong possiblities have been identified by this process.
Understanding genetic differences in alcohol action also requires information about the neuropharmacology of the drug. Only recently have we begun to understand which synaptic signaling systems are affected by alcohol. Faculty within the Department of Pharmacology are leaders in this area showing actions of ethanol on the excitatory glutamate receptors (NMDA, AMPA, and kainate subtypes) and the inhibitory GABA and glycine receptors.
The Department of Pharmacology and its integration of pharmacologists, classical geneticists, molecular biologists, electrophysiologists, and neurochemists is entering a new era with the hope that the most exciting times are yet to come and that the molecular and genetic mechanisms of alcohol intoxication, tolerance, and dependence will be revealed in much greater detail in the future.
Primary Faculty
Hoffman, Paula L. Neuropharmacology; mechanisms of alcohol tolerance, dependence, and craving; genetic aspects of alcohol dependence and affective disorders; biochemical/molecular biological/genetic analysis of CNS receptors and signal transduction systems
Sikela, James M. Neurogenomics; disease gene discovery; human genome evolution and variation
Tabakoff, Boris Molecular pharmacology; pharmacogenetics; neuroadaptation and neurotransmitter metabolism/enzymology; CNS receptor molecular pharmacology and genetics/genomics of addiction
Zahniser, Nancy R. Regulation of dopamine transporters; mechanisms underlying cocaine’s actions; neurotransmitter receptors and release in brain
Secondary Faculty
Leonard, Sherry S. Molecular neurobiology of nicotine addiction in mental illness