Effect of quinine on autoreceptor-regulated serotonin release in the rat hippocampus.
The involvement of K+ channels in the autoregulation of terminal serotonin (5-hydroxytryptamine, 5-HT) release was investigated by microdialysis in the hippocampus of conscious rats. Extracellular 5-HT was increased concentration-dependently by the K+ channel blocker quinine (10, 100 and 1000 microM in perfusate), and tetrodotoxin (10 microM) but not fluoxetine (5 microM) exerted a partially attenuating influence. The 5-HT1/2/6 receptor antagonist methiothepin (50 microM) increased dialysate 5-HT, most likely through 5-HT1B autoreceptors tonically activated in the hippocampus of awake rats as opposed to the previously reported lack of effect 5-HT1B autoreceptor blockade in anesthetized rats. The effect of methiothepin was greatly reduced by preperfusion with quinine (100 microM), consonant with a role for quinine-sensitive K+ channels in the autoregulation of 5-HT release in the hippocampus by 5-HT receptor antagonism. In contrast, the reduction in dialysate 5-HT induced by the 5-HT1 receptor agonist RU 24969 (1 microM), in the presence of fluoxetine (5 microM), persisted in the co-presence of quinine, consonant with the involvement of (extrasynaptic?) 5-HT autoreceptors not coupled with quinine-sensitive K+ channels.
Li
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Department of Biomedical and Therapeutic Sciences, College of Medicine, University of Illinois, Peoria 61656, USA.
Reith
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D000818:Animals; D017660:Autoreceptors / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D017551:Microdialysis; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011803:Quinine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D017660:Autoreceptors; D005473:Fluoxetine; D007211:Indoles; D008719:Methiothepin; D015221:Potassium Channels; D011803:Quinine; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013779:Tetrodotoxin; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole