Document Detail

Interaction of serotonin autoreceptor antagonists in the rat dorsal raphe nucleus: an in vitro fast cyclic voltammetry study.
MedLine Citation:
PMID:  11172936     Owner:  NLM     Status:  MEDLINE    
5-HT1A, 5-HT1B and 5-HT1D receptors are known to function as 5-HT autoreceptors in the rat dorsal raphe nucleus (DRN), modulating local 5-HT efflux. However, there are no studies on the simultaneous blockade of these receptors in the DRN. We investigated the effect of 5-HT1B and 5-HT1D receptor antagonists on 5-HT efflux in rat DRN, alone and in the presence of 5-HT1A receptor antagonists, using the technique of fast cyclic voltammetry. The 5-HT1A receptor antagonist, WAY 100635, and the 5-HT1B receptor antagonist, SB-224289, had no effect on 5-HT efflux while the 5-HT1B/1D receptor antagonist, GR 127935, produced a small decrease in 5-HT efflux. In contrast, the 5-HT1D receptor antagonist, BRL 15572, produced a significant increase in 5-HT efflux. Co-perfusion of WAY 100635 and SB-224289 significantly increased 5-HT efflux. In addition, WAY 100635 reversed the small inhibition of 5-HT efflux observed with GR 127935 but had no effect on the BRL 15572-induced increase. Antagonism of all three 5-HT autoreceptors with SB-224289, BRL 15572 and WAY 100635 significantly increased 5-HT efflux. These data confirm that 5-HT efflux within the DRN is under the control of 5-HT1A, 5-HT1B and 5-HT1D autoreceptors and elevation of 5-HT efflux was greatest following antagonism of 5-HT1A and 5-HT1B receptors.
C Roberts; G W Price
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuroscience letters     Volume:  300     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-05-10     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  45-8     Citation Subset:  IM    
Department of Neuroscience Research, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Essex, CM19 5AW, Harlow, UK.
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MeSH Terms
Drug Interactions
Electric Stimulation
Raphe Nuclei / drug effects*
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1B
Receptor, Serotonin, 5-HT1D
Receptors, Serotonin / drug effects,  metabolism*
Receptors, Serotonin, 5-HT1
Serotonin Antagonists / pharmacology*
Reg. No./Substance:
0/Receptor, Serotonin, 5-HT1B; 0/Receptor, Serotonin, 5-HT1D; 0/Receptors, Serotonin; 0/Receptors, Serotonin, 5-HT1; 0/Serotonin Antagonists

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