Effect of Middle Cerebral Artery Occlusion on Serotonin Metabolism in Rat Brain

Abstract

Previously the authors have studied local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) in rats 1 hour after the occlusion of the left middle cerebral artery. It was found that LCGU was decreased in the ipsilateral cerebral cortex and the lateral striatum, where LCBF was also reduced. On the other hand, LCGU was increased in the ipsilateral medial striatum, olfactory tubercle, globus pallidus, subthalamic nucleus, and lateral habenula. They have also investigated changes in catecholamine metabolism in these regions and found very close relationship between LCGU, LCBF, and dopamine metabolism. In the present work, changes in serotonin metabolism were investigated measuring tryptophan (TRP), serotonin (5-hydroxytryptamine, 5-HT), and its metabolite, 5-hydroxy-indoleacetic acid (5-HIAA) in certain regions of the cerebral cortex, basal ganglia, and brain stem using the same ischemic model rats. The results were compared with the changes in LCGU and LCBF. The concentration of TRP was significantly increased in the “ischemic” regions, such as the ipsilateral cerebral cortex and lateral striatum. On the other hand, 5-HT was significantly decreased not only in the “ischemic” regions but also in the “nonischemic” regions such as the globus pallidus. There was a tendency for 5-HT to decrease in the ipsilateral substantia nigra and raphe nuclei. 5-HIAA showed no significant change in the “ischemic” regions but was significantly increased in the globus pallidus and raphe nuclei and had a tendency to increase in the substantia nigra. There was no significant change in any of these parameters in the regions of the contralateral side. The changes in 5-HT metabolism in the “ischemic” regions, such as the ipsilateral cortex and lateral striatum indicate that the synthesis of 5-HT was reduced, but its release was unchanged. Increase in 5-HT metabolism in the “nonischemic” regions, such as the globus pallidus, substantia nigra, and raphe nuclei indicates a presence of neuronally-mediated biochemical diaschisis.