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p‐Chlorophenylalanine Increases Tryptophan‐5‐Hydroxylase mRNA Levels in the Rat Dorsal Raphe: A Time Course Study Using In Situ Hybridization

Abstract: The effects of a single dose of p‐chlorophenylalanine on the mRNA encoding tryptophan‐5‐hydroxylase (EC 1.14.16.4) in the rat dorsal raphe nucleus were analyzed using in situ hybridization. The levels of tryptophan‐5‐hydroxylase mRNA were markedly increased in cell bodies located in the ventromedial part of the dorsal raphe 1–2 days after p‐chlorophenylalanine (300 mg/kg, i.p.) administration. This was followed by a decrease in the amount of tryptophan‐5‐hydroxylase mRNA, which returned to basal values by 5 days after treatment. An almost symmetric time course was observed for the midbrain serotonin concentration. Our results on the temporal pattern of changes in tryptophan‐5‐hydroxylase mRNA levels in the ventromedial part of the dorsal raphe are opposite to those reported for the enzyme activity and serotonin concentration after p‐chlorophenylalanine treatment. These changes may result from modifications in enzyme mRNA expression, suggesting that tryptophan‐5‐hydroxylase gene transcription is involved in feedback mechanisms regulating serotonin synthesis.