Some factors influencing the release of 5-hydroxyindol-3-ylacetic acid in the forebrain.

1. Electrical stimulation of the mid-brain raphé in anaesthetized adrenalectomized rats produced a significant decrease in the forebrain content of 5-hydroxytryptamine (5-HT) and an increase in the concentration of 5-hydroxyindol-3-ylacetic acid (5-HIAA).2. Stimulation of peripheral sensory nerves did not influence either the forebrain content of 5-HIAA or the efflux of 5-HIAA from the cerebral cortex.3. Probenecid (200 mg/kg) caused a twofold increase in 5-HIAA content of the rat's forebrain, while the efflux of 5-HIAA from the cerebral cortex remained unchanged.4. Stimulation of the mid-brain raphé in animals pretreated with probenecid does not produce the rise in the forebrain levels of 5-HIAA seen in stimulated untreated controls and does not affect the efflux of 5-HIAA from the cerebral cortex.5. In preliminary experiments, lysergic acid diethylamide (LSD 25) substantially reduced and/or prevented the increase in the release of 5-HIAA in the forebrain observed in untreated animals with raphé stimulation.