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PubMed · 9652362

Differential regional antagonism of 8-OH-DPAT-induced decrease in serotonin synthesis by two 5-HT1A receptor antagonists.

L G Larsson·C Stenfors·S B Ross
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Abstract

The effects of two 5-HT1A receptor antagonists, (R)-3-N, N-dicyclobutylamino-8-fluoro-3,4-dihydro-2 H-1-benzopyran-5-carboxamide hydrogen (2 R,3 R)-tartrate monohydrate (NAD-299) and N-(2-(1-(2-methoxyphenyl)-piperazinyl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) on the decrease in 5-hydroxytryptophan (5-HTP) accumulation evoked by (RS)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene (8-OH-DPAT) in rats treated with the decarboxylase inhibitor, 3-hydroxyphenylhydrazine (NSD 1015) were studied in four rat brain regions: hippocampus, hypothalamus, striatum and frontal cortex. Dose-response studies revealed differential effects of both antagonists in the areas examined. Both antagonists were significantly more potent in antagonising the effect of 0.30 and 0.76 micromol/kg s.c. 8-OH-DPAT in hippocampus than in hypothalamus, striatum and frontal cortex in mentioned order. This order of potency was the opposite to that found for 8-OH-DPAT in decreasing the 5-HTP accumulation. Since previous studies by others have indicated that the reserve of somatodendritic 5-HT1A receptors is greater in dorsal raphe nucleus innervating frontal cortex and striatum than in median raphe nucleus which mainly innervates hippocampus, the observed different regional potency of the two 5-HT1A receptor antagonists may be explained by this difference in the 5-HT1A receptor reserve.

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8-Hydroxy-2-(di-n-propylamino)tetralinAnimalsBenzopyransBrain ChemistryDose-Response Relationship, DrugHippocampusHypothalamusMaleNeostriatumPiperazinesPrefrontal CortexPyridinesRatsRats, Sprague-DawleySerotoninSerotonin AntagonistsSerotonin Receptor AgonistsJournal Article

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L G Larsson, C Stenfors, S B Ross. 1998-04-10. Differential regional antagonism of 8-OH-DPAT-induced decrease in serotonin synthesis by two 5-HT1A receptor antagonists.. https://doi.org/10.1016/s0014-2999(98)00073-9

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