The 5‐HT1 receptor agonist RU‐24969 decreases 5‐hydroxytryptamine (5‐HT) release and metabolism in the rat frontal cortex in vitro and in vivo

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Abstract
K+‐stimulated release of [3H]‐5‐hydroxytryptamine ([3H]‐5‐HT) from rat frontal cortex slices was decreased by the 5‐HT receptor agonists 5‐methoxy‐n1N‐dimethyltryptamine and 5‐methoxy‐3(1,2,3,6,‐tetrahydro‐4‐pyrindinyl)‐1H‐indole (RU‐24969) (1 × 10−5 M). RU‐24969 (10 mg kg−1, i.p.) decreased extracellular 5‐HT and its metabolite 5‐hydroxyindoleacetic acid measured in vivo by use of intracerebral dialysis combined with high performance liquid chromatography and electrochemical detection. The decrease in extracellular 5‐hydroxyindoleacetic acid in vivo after RU‐24969 (10 mg kg−1, i.p.) was also observed by in vivo voltammetry. The non‐selective 5‐HT antagonist metergoline prevented the RU‐24969‐induced decrease in 5‐HT release and metabolism in vivo while the 5‐HT2 receptor antagonist R‐55669 (ritanserin) did not. The results support the view that RU‐24969 stimulates a 5‐HT1 receptor that is involved in the autoregulation of 5‐HT release and metabolism.

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