The authors conducted an in vivo study, using a rat striatal ischemic model, of the effect of GABAergic transmission upon the
dopamine synthesizing
enzyme tyrosine hydroxylase in the neurons of the substantia nigra pars compacta. Two hours transient
middle cerebral artery occlusion produced massive striatal ischemic damage resulting in a marked decrease of GABAergic projection to the ipsilateral substantia nigra. Histological examinations were conducted in rats killed at three, seven, 15, 30 and 94 days after
ischemia. The immunoreactivity for
tyrosine hydroxylase in the ipsilateral pars compacta was unaltered up to three days after the ischemic insult, but it was markedly decreased at seven days post-
ischemia. At this stage, the number of neurons positive for
tyrosine hydroxylase was significantly decreased in the ipsilateral pars compacta, whereas there was no significant reduction in the number of pars compacta neurons containing Nissl substance. By 30 days post-
ischemia, the
tyrosine hydroxylase-positive cell number in the ipsilateral pars compacta appeared to be equivalent to that of the contralateral side. It was also noted that continuous intraventricular administration of a GABAA receptor agonist
muscimol, initiated from 24 h post-
ischemia, effectively prevented the transient reduction of immunoreactivity for
tyrosine hydroxylase in the ipsilateral pars compacta at seven and 15 days after ischemic insult. The present study revealed that the striatal ischemic lesion induced a transient down-regulation of
tyrosine hydroxylase synthesis in the pars compacta neurons, which could be prevented by administration of
GABA agonist, suggesting that GABAergic transmission greatly affects
dopamine metabolism in these cells.