INCREASED SEROTONIN TURNOVER IN CORPUS STRIATUM FOLLOWING AN INJECTION OF KAINIC ACID - EVIDENCE FOR NEURONAL FEEDBACK REGULATION OF SYNTHESIS

Kainic acid, a cyclic analog of glutamate, has been reported by other investigators to reduce the number of serotonin (5HT) binding sites in rat striatum following an intrastriatal injection. We found that kainic acid injected into the striatum caused a dose-dependent increase in ipsilateral striatal 5-hydroxyindoleacetic acid (5HIAA) content, while not affecting the level of 5HT. There was no detectable change in 5HT metabolism in the contralateral striatum. The increase of 5HIAA was a reflection of increased 5HT turnover in the injected striatum as measured from the decline of 5HIAA after pargyline treatment or the rise of 5-hydroxytryptophan after benserazide treatment. There was also a concomitant increase of tryptophan hydroxylase activity. Kainic acid treatment resulted in an apparent decrease of the Kmand increase of the Vmax for the pteridine cofactor and an increase of the Vmax for tryptophan by tryptophan hydroxylase. Kainic acid injection into the dorsal raphe nucleus caused a dose-dependent decrease in 5HT content of the dorsal raphe nucleus and in both striata, which are dorsal raphe nucleus projection areas. Our results suggest that 5HT formation in the striatum is normally modulated by an inhibitory neuronal feedback loop. Interruption of the loop by injecting kainic acid causes 5HT formation and tryptophan hydroxylase activity to increase in the ipsilateral but not contralateral striatum. Kainic acid apparently destroys 5HT neurons when injected close to the cell soma. © 1979 Springer-Verlag.