University of Virginia Health System

Central catecholamine dysfunction has been implicated in the pathophysiology of major psychiatric disorders (such as schizophrenia and depression) and neurological disorders (such as Parkinson's disease). For years, studies of the neurobiology of and therapeutic treatments for schizophrenia and Parkinson's disease have focused primarily on dopamine and dopaminergic drugs. Although relatively effective, treatment of these diseases has historically been plagued by the debilitating extrapyramidal side effects of available drugs. In an attempt to better understand the etiology of these diseases and in the search for novel therapeutic strategies, interest has shifted toward examining the interaction of monoamines and their role in regulating the functional activity of dopamine neurons. My research is focused on identifying the cellular substrates for the physiological actions of catecholaminergic transmitters and on whether there is a cellular basis for the functional interactions between monoaminergic transmitters. Toward this end we have developed antibodies directed against alpha2-adrenergic receptors and adenosine receptors for use in immunohistochemical mapping of these receptors in the rat brain. Using these reagents and commercially available antibodies for other catecholaminergic neurons and their receptors, we can employ a variety of dual labeling techniques to identify the neuronal elements that are implicated in major affective disorders. Our studies will examine the possibility that monoamines (and their respective receptors) exist in specific anatomical circuits that enable reciprocal modulation of neuronal activity, and further, that these interactions may be mediated by specific receptor subtypes.