[Pharmacological characterization of alpha 2-adrenoceptor regulated 5-HT release in the rat hippocampus].
The purpose of the present study is to confirm the functional regulation of alpha 2-adrenoceptor on the release of serotonin (5-HT) from the rat hippocampus in vivo. Under several pharmacological conditions, extracellular levels of 5-HT were estimated by assaying its concentrations in the perfusion fluid through the use of high-performance liquid chromatography with electrochemical detection. Extracellular 5-HT in the hippocampus was reduced by tetrodotoxin, 10 microM co-perfusion and was increased by perfusion with a selective 5-HT reuptake inhibitor, fluoxetine, 10 microM. Addition of potassium (K+; 120 mM) to the perfusion fluid evoked an approximately 3-fold increase in 5-HT release, and a calcium free medium completely prevented this K(+)-evoked 5-HT release. Potassium-evoked 5-HT release from the hippocampus of freely moving rats was significantly and concentration-dependently inhibited when alpha 2-adrenoceptor agonist, UK14,304, 0.1 microM to 10 microM was added to the perfusion solution, while the output of a 5-HT major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), remained unchanged. This action of UK14,304 was prevented by pretreatment with idazoxan, 5 mg/kg, i. p., an alpha 2-adrenoceptor antagonist. In rats that were catecholaminergically denervated with 6-hydroxydopamine, UK14,304, 10 microM also inhibited the potassium-evoked 5-HT release, but had no effect on the 5-HIAA output. The UK14,304-induced inhibition of 5-HT release was prevented by pretreatment with pertussis toxin (PTX). These findings suggest that 5-HT release is functionally modulated via alpha 2-adrenoceptors located on the serotonergic nerve terminals in the rat hippocampus. They also indicate the possibility that the inhibition of 5-HT release via alpha 2-adrenoceptors is linked to G-proteins which are substrates of PTX.
Numazawa
R
R
Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo, Japan.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D019329:Idazoxan; D017551:Microdialysis; D011810:Quinoxalines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D012701:Serotonin; D000068438:Brimonidine Tartrate; D019204:GTP-Binding Proteins; D019329:Idazoxan