Hippocampal pyramidal cell response to 6-hydroxydopamine lesions of the rat ventral tegmental area

The occurrence of neurofibrillary tangles (NFT) in the perforant pathway in association with dopaminergic cell loss in the ventral tegmental area (VTA) in human mesolimbic dementia, raises the possibility that denervation is a cause of NFT formation. This was tested in the rat by lesioning dopaminergic neurons which project to the hippocampus from the ventral tegmental area by means of stereotaxic injections of 6-hydroxydopamine. This resulted in the appearance of immunoreactivity to the paired helical filament protein plus an increase of tau and MAP-2 proteins in pyramidal neurons of CA-1 and CA-2. These neuronal responses to dopaminergic denervation are consistent with a precursor stage to NFT development.