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.
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 X 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.
Brazell
M P
MP
Marsden
C A
CA
Nisbet
A P
AP
Routledge
C
C
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D004563:Electrochemistry; D005625:Frontal Lobe / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D007211:Indoles; D011985:Receptors, Serotonin; D008711:Metergoline; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid