Long-term local and distal increases in tryptophan hydroxylase activity following intracerebral kainic acid injections in the rat

Abstract

The administration of kainic acid (1–2 μg) into the right striatum of adult rats resulted in a marked local increase in tryptophan hydroxylase activity (+ 54–106%). This change was significant as soon as on the second day after the treatment and persisted for at least 12 days. In addition, long-lasting elevations of tryptophan hydroxylase activity were also observed in the anterior raphe area, septum and ipsilateral hippocampus and cerebral cortex. In contrast, the intrahippocampal injection of kainic acid (1 μg) induced a long-term increase in tryptophan hydroxylase activity only in the injected structure. In all cases, the changes in tryptophan hydroxylase activity were associated with significant increases in the V max of the enzyme with no alteration of its apparent affinities for tryptophan and the pterin cofactor. Studies of the sensitivity of tryptophan hydroxylase from control and from kainic acid-treated rats to in vitro activating conditions (Ca +-dependent phosphorylation, partial trypsinization, exposure to sodium dodecyl sulfate) suggest that the intrastriatal injection of the neurotoxin induced a long-lasting activation of the enzyme. These findings indicate that intracerebral injections of kainic acid may be a valuable approach to explore further the mechanisms controlling tryptophan hydroxylase activity in vivo.