The novel 5-HT1A receptor antagonist (S)-UH-301 prevents (R)-8-OH-DPAT-induced decrease in interstitial concentrations of serotonin in the rat hippocampus.

G G Nomikos; L Arborelius; T H Svensson

doi:10.1016/0014-2999(92)90433-5

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The novel 5-HT1A receptor antagonist (S)-UH-301 prevents (R)-8-OH-DPAT-induced decrease in interstitial concentrations of serotonin in the rat hippocampus.

G G Nomikos·L Arborelius·T H Svensson

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Abstract

Previous studies have demonstrated that the novel 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) analogue (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin ((S)-UH-301) is able to antagonize several behavioural and biochemical effects of the 5-HT1A receptor agonist 8-OH-DPAT in the rat. In the present study in vivo microdialysis was used to evaluate the effects of (S)-UH-301 on interstitial concentrations of 5-hydroxytryptamine (5-HT), its metabolite 5-hydroxyindoloacetic acid (5-HIAA), and the catecholamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the dorsal hippocampus of freely moving rats. Furthermore, the effects of (S)-UH-301 on (R)-8-OH-DPAT-induced changes in dialysate hippocampal concentrations of 5-HT and metabolites were examined. Neither 5-HT nor metabolites were significantly influenced by (S)-UH-301 (1.25, 2.5, 5.0 mg/kg s.c.). In contrast, (R)-8-OH-DPAT (100 micrograms/kg s.c.) decreased interstitial concentrations of 5-HT (to 45% of baseline) and 5-HIAA (to 75%), and increased concentrations of DOPAC (to 165%) and HVA (to 155%). Pretreatment with (S)-UH-301 (2.5 mg/kg s.c.) 20 min before (R)-8-OH-DPAT (100 micrograms/kg s.c.) abolished the 5-HT and metabolite response to (R)-8-OH-DPAT. These data indicate that (S)-UH-301 is able to antagonize (R)-8-OH-DPAT-induced biochemical effects in vivo without producing any effects when given alone. Thus, the present study contributes to the characterization of (S)-UH-301 as a 5-HT1A receptor antagonist with low intrinsic activity.

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8-Hydroxy-2-(di-n-propylamino)tetralin Analysis of Variance Animals Dialysis Hippocampus Male Rats Rats, Wistar Serotonin Serotonin Antagonists Stereoisomerism Journal Article Research Support, Non-U.S. Gov't

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G G Nomikos, L Arborelius, T H Svensson. 1992-06-17. The novel 5-HT1A receptor antagonist (S)-UH-301 prevents (R)-8-OH-DPAT-induced decrease in interstitial concentrations of serotonin in the rat hippocampus.. https://doi.org/10.1016/0014-2999(92)90433-5

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