Estimation of apparent pA2 values for WAY 100635 at 5-HT(1A) receptors regulating 5-hydroxytryptamine release in anaesthetised rats

Marie Bernadette Assié, Wouter Koek

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


5-HT(1A) receptor agonists decrease 5-hydroxytryptamine (5-HT) terminal release by activating somatodendritic 5-HT(1A) autoreceptors. The selective 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635) inhibits these effects of 5-HT(1A) receptor agonists. The present study was aimed at estimating apparent pA2 values for WAY 100635 to antagonise 5-HT(1A) receptor agonist-induced decrease in 5-HT release in rat hippocampus. Extracellular concentrations of 5-HT were measured in microdialysis samples after administration of cumulative doses of 5-HT(1A) receptor agonists with different intrinsic activity, alone or in the presence of increasing doses of WAY 100635. Administration of cumulative doses of (±)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.01-40 mg/kg), 1[2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphtyl)piperazine (S 14506) (0.00063-2.5 mg/kg), or buspirone (0.16-40 mg/kg), dose-dependently decreased the extracellular concentrations of 5-HT in the ventral hippocampus. Pre-treatment with WAY 100635 (0.01-0.63 mg/kg) shifted the dose-response curve of each agonist to the right in a dose-dependent manner. WAY 100635 antagonised the effects of all three compounds in a competitive manner, with an estimated apparent in vivo pA2 value of 7.95 (95% confidence limits: 7.66-8.24). Taken together, the results are evidence that buspirone, S 14506 and 8-OH-DPAT, administered in cumulative doses, decreased 5-HT release by activating similar 5-HT(1A) receptors, because a common apparent pA2 value was obtained for WAY 100635. The results also show that orderly microdialysis data can be obtained using cumulative dosing, which enables one to collect dose-response data rapidly, with fewer animals. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)173-177
Number of pages5
JournalEuropean Journal of Pharmacology
Issue number2
StatePublished - Dec 8 2000
Externally publishedYes


  • 5-HT (5-hydroxytryptamine, serotonin) release
  • 5-HT(1A) receptor
  • Microdialysis
  • WAY 100635
  • in vivo

ASJC Scopus subject areas

  • Pharmacology


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