Core - Quantitative Autoradiography

Boyson, Sally

Abstract

This core will be responsible for quantitative autoradiographic studies of D1 and D2 dopamine receptors in the rats bearing allografted chromaffin cells or ventral mesencephalon, as well as rats xenografted with human ventral mesencephalon. All of these rats will also have been studied for changes in electrophysiology, electrochemistry, and/or rotational behavior by one or more of the projects. We will test the hypothesis that dopamine receptor alterations are responsible for the functional supersensitivity to dopamine agonists seen on the asymmetric rotational behavior with administration of amphetamine or apomorphine. The Core will plan and execute chronic drug administration protocols, for all projects, to study the effects of direct and indirect dopamine agonists on the survival and functioning of the grafts. We will study selective D1 and D2 agonists administered separately or together. We will compare the effects of these direct agonists with those of the dopamine precursor therapy L- dopa/carbidopa (which results in stimulation of both D1 and D2 receptors). We will also compare the effects of L-dopa/carbidopa, which will increase levels of dopamine and dopamine metabolites, with selegiline (deprenyl), an MAO-inhibitor which prolongs the life of dopamine and decreases the oxidative metabolites of dopamine, since there is suspicion that the oxidative metabolites of dopamine directly injure the dopaminergic neuron.