THE 5-HT1 RECEPTOR AGONIST RU-24969 DECREASES 5-HYDROXYTRYPTAMINE (5-HT) RELEASE AND METABOLISM IN THE RAT FRONTAL-CORTEX INVITRO AND INVIVO

1 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 .times. 10-5 M). 2 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. 3 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. 4 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. 6 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.