In vivo release of catecholamines from xenogeneic chromaffin cell grafts with antidepressive activity

Previous studies in our laboratory have demonstrated that allografts of adrenal medullary tissue and xenografts of isolated bovine chromaffin cells to the rat frontal cortex can increase antidepressive activity in two separate animal models. Biochemical and pharmacological evidence suggest that the most likely mechanism of these antidepressive effects is via local release of catecholamines into the surrounding cortical parenchyma. The aim of the present study was to directly characterize the antidepressive mechanism of chromaffin cell xenografts by utilizing in vivo microdialysis to measure extracellular catecholamine levels from bovine chromaffin cell and control implanted rat frontal cortex. Following transplantation, only bovine chromaffin cell grafted rats displayed significant increases in antidepressive activity, as assessed by the forced swimming test, compared to rats with grafts of bovine adrenal medullary fibroblasts or nontransplanted rats. In vivo microdialysis results revealed remarkably elevated levels of epinephrine (EPI) and norepinephrine (NE), but not dopamine, in dialysates from bovine chromaffin cell-transplanted frontal cortex. The most likely source of these enhanced EPI and NE levels is the grafted xenogeneic chromaffin cells. The results of this study directly demonstrate that xenografts of bovine chromaffin cells to the rat frontal cortex provide a releasable pool of catecholamines for antidepressive activity.