The influence of the subthalamic nucleus upon the damage to the dopamine system following lesions of globus pallidus in rats

Lesioning or stimulating the subthalamic nucleus (STN) in patients with Parkinson's disease, or in animal models of parkinsonism, alleviates many of the symptoms and so it is tempting to think of the STN as a part of the cause of Parkinson's disease. The globus pallidus (GP) is thought to have a tonic inhibitory action on the STN. An ibotenic acid injection into the GP in rats removes the cells of the GP and, over the following 6 weeks, a progressive loss of dopamine cells (counted stereologically in sections stained for tyrosine hydroxylase) develops in substantia nigra (SN). In this investigation we show that, when animals have the STN cells destroyed by very small ibotenic acid injections, their dopamine neurons are not damaged. Furthermore, if a lesion to the GP follows a lesion of STN then the dopamine cells also survive this double insult, at least for the first 3 weeks following the lesion. The experiments provide good reason to suspect that, at least in the short term, increased activity in the STN is a contributory cause of the loss of dopamine cells which follows the lesion of the GP in rats. Whether or not this is part of the mechanism of cell loss in Parkinson's disease, the rats with GP lesions at least provide an opportunity to test strategies that might protect dopamine cells from slowly developing damage. Removing the STN seems to be neuroprotective in this new model of dopamine degeneration.