Chromaffin cell xenografts in the rat neocortex can produce antidepressive activity in the forced swimming test

Adrenal medullary allografts, as well as other monoaminergic tissues, have been demonstrated in our laboratory to increase antidepressive activity when transplanted into the frontal neocortex of rats. Refinement in the optimal parameters for xenograft viability has indicated that isolated bovine chromaffin cells may be an improved source of graft donor tissue. The aim of the present study was to determine whether isolated bovine chromaffin cell grafts to the rat frontal neocortex could provide an alternative source of catecholamines for antidepressant activity. Isolated bovine chromaffin cells, isolated bovine fibroblasts, or an equal volume of vehicle were unilaterally implanted into the right or left frontal cortex or right visual cortex. All rats were assessed before and 6 weeks after transplantation using the forced swimming test, a popular measure of antidepressant activity. Bovine chromaffin cell grafts in either the right or left frontal cortex produced significant increases in antidepressant activity compared to grafts of bovine fibroblasts and sham-operated or nontransplanted rats. In contrast, bovine chromaffin cells transplanted to the visual cortex did not affect antidepressant activity. Bovine fibroblast grafts in the frontal cortex also induced slight increases in antidepressant activity, although significantly less than chromaffin cell grafts. Morphological analysis revealed robust survival of tyrosine hydroxylase-positive chromaffin cells that retained their in situ ultrastructure and occasionally formed synaptic connections with the host parenchyma. These results suggest that xenografted isolated bovine chromaffin cells can provide a viable source of catecholamines for antidepressive activity.