Neurobiology of Opioid and Dopamine Systems

Our research is broadly focused on the regulation and function of central dopaminergic and opioid systems utilizing the techniques of behavioral, cellular, and molecular neurobiology and pharmacology. Central opioid and dopaminergic systems together play a collective role in regulating locomotor activity and reinforcement. Ongoing studies involve characterizing various aspects of the relationship between central opioid and dopaminergic systems, determining how these systems regulate elements of each other, including factors that control expression of related genes, and investigating hoe the two systems interact to modulate signal transduction in specific brain regions. Certain results from these studies have shown that exposure to cocaine, an indirect dopamine receptor agonist, has profound effects on the expression and function of opioid receptors, dopamine receptors, opioid peptides, and related genes and second messenger systems in several brain regions. In addition to elucidating mechanisms that underlie the regulation of the endogenous opioid system, we have identified neurobiological alterations that occur during exposure to cocaine, which may help to ascertain molecular mechanisms of drugs addiction.

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Representative Publications:

• Unterwald EM, Horne J, and Kreek MJ. Chronic cocaine alters brain mu opioid receptors. Brain Res 584 314-318 (1992)
• Unterwald EM, Cox BM, Kreek MJ, Cote TE, and Izenwasser S. Chronic repeated cocaine administration alters basal and opioid-regulated adenlyl cyclase activity. Synapse 15 33-38 (1993)
• Unterwald EM, Ho A, Rubenfeld JM, and Kreek MJ. Time course of the development of sensitization and dopamine receptor regulation during binge cocaine administration. J Pharmacol Exp 270 1387-1397 (1994)
• Unterwald EM, Rubenfeld JM, and Kreek MJ.Repeated cocaine administration upregulates K and u , but not s , opioid receptor. Neuroreport 5 1613-1616 (1994)