William J. Shoemaker, Ph.D.
Associate Professor

Dr. Shoemaker, a basic neuroscientist, investigates the neurobiology of emotion and how chronic drug exposure and stress effects neuronal circuits in the limbic system. These brain pathways utilize norepinephrine, serotonin, dopamine, the endogenous opioids and other substances as transmitters. These same pathways are also activated by psychoactive drugs. Dr. Shoemaker is exploring the connection between early life stresses and later reactivity to stress and the propensity to self-administer drugs of abuse. This stress sensitization process can endure for months or years and can be considered as a memory function of the emotional circuits. These studies are carried out in rats and mice, and include techniques that allow monitoring of neurochemical events in the brain of awake, freely moving animals using in vivo microdialysis and assays for these transmitters. Using neuroanatomical measures, he has demonstrated that early life stress alters the structure of the brain, and, that this altered structure may be permanent. A second focus involves the use of a specific gene knockout mutations in mice. In one study, the fgf receptor 2 in mice was conditionally knocked out. This mutation produces mice that are hyperactive and hyperexcitable. We have gathered evidence demonstrating that the enhanced activity of the dopamine systems is responsible for the behavioral hyperactivity. The fgf growth factor is highly enriched in the ventral tegmental area of the midbrain (VTA) and studies are underway to determine how the receptor mutation alters the dynamics of the VTA-mesolimbic dopamine pathway. Another preparation allows the study of prenatal exposure to ethanol. This is a rodent model of Fetal Alcohol Syndrome. In all of these studies, a major objective is determining adaptation at the neuronal level and at the level of gene expression to the chronic drug exposure or stress.