The effects of a 5-HT1A receptor agonist and antagonist on the 5-hydroxytryptamine release in the central nucleus of the amygdala: a microdialysis study with flesinoxan and WAY 100635.
The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 microM tetrodotoxin (TTX), 60 mM K+ and perfusion with Ca(2+)-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration of 300 nM of RU 24969, a 5-HT1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic administration of the 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular 5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT1A receptors.
Bosker
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F
Department of Psychiatry, University Hospital Utrecht, The Netherlands.
Vrinten
D
D
Klompmakers
A
A
Westenberg
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D010879:Piperazines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D007211:Indoles; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; C056895:flesinoxan; D013779:Tetrodotoxin; D011189:Potassium Chloride; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin