Adrenal medulla grafts in the hemiparkinsonian rat: profile of behavioral recovery predicts restoration of the symmetry between the two striata in measures of pre- and postsynaptic dopamine function

Abstract

Following unilateral striatal dopamine depletion, the hemiparkinsonian rat exhibits rotational behavior in response to amphetamine and apomorphine. The rotational behaviors induced by these drugs are thought to reflect an asymmetry in presynaptic striatal dopamine release and an asymmetry in postsynaptic striatal dopamine receptor function, respectively. Grafts of adrenal medulla cells in the lateral ventricle of hemiparkinsonian rats have been reported to reduce behavioral asymmetry. More than one profile of behavioral recovery, however, is observed. Some animals show a graft-induced decrease only in the response to apomorphine, but others show a decrease in the response to amphetamine, and still others show a decrease in the behavioral responses to amphetamine and apomorphine. In this report, amphetamine- and apomorphine-induced turning behaviors were determined in hemiparkinsonian rats prior to and following intraventricular grafts of adrenal medulla or control tissue. Both bilateral intrastriatal microdialysis in freely moving animals and quantitative dopamine receptor autoradiography procedures were conducted in each animal so as to determine the relations between pre- and postsynaptic dopaminergic measures as well as the association between these measures and the different profiles of behavioral recovery after adrenal medulla grafts. We report here that in animals with an adrenal medulla graft-induced decrease in the behavioral response to amphetamine, the balance between the two striata in extracellular striatal dopamine concentrations and D2 dopamine receptor binding was restored. Furthermore, enhanced extracellular striatal dopamine concentrations were highly correlated with the graft-induced symmetry in striatal D2 dopamine receptor binding. In contrast to animals with decreased amphetamine-induced turning, in animals with a graft-induced decrease exclusively in response to apomorphine, the presynaptic symmetry was not restored and there was a significantly smaller effect on D2 receptor binding. We conclude that those animals that show decreased amphetamine-induced turning after adrenal medulla grafts had the most effective grafts, and suggest that methods designed to optimize this behavioral profile are most likely to lead to enhanced clinical efficacy with this procedure.