Synergistic neurochemical and behavioral effects of fluoxetine and 5-HT1A receptor antagonists

Eur J Pharmacol. 1998 Sep 18;357(2-3):179-84. doi: 10.1016/s0014-2999(98)00590-1.

Abstract

We studied the ability of WAY 100635 [N-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide], 0.5 mg/kg, i.v. and (-)-5-Me-8-OH-DPAT [(-)-5-methyl-8-hydroxy-2-(di-n-propylamino)tetralin], 3 mg/kg, i.v. two selective 5-HT1A receptor antagonists, to potentiate: (1) the enhancement of extracellular 5-HT levels ([5-HT(ext)]) induced by a single administration of 5 mg/kg i.p. fluoxetine using in vivo microdialysis in the ventral hippocampus of conscious rats, (2) the decrease in food intake induced by this antidepressant drug in food-deprived rats. The effects of fluoxetine were significantly potentiated, by 30-40%, by WAY 100635 as well as by (-)-5-Me-8-OH-DPAT in the two sets of experiments. Thus, fluoxetine increased [5-HT(ext)] in serotonergic nerve terminal areas and consequently, induced hypophagia, both effects being limited by indirect activation of somatodendritic 5-HT1A autoreceptors.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / analogs & derivatives
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Analysis of Variance
  • Animals
  • Chromatography, High Pressure Liquid
  • Drug Synergism
  • Eating / drug effects*
  • Fluoxetine / pharmacology*
  • Hippocampus / metabolism*
  • Male
  • Microdialysis
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin*
  • Receptors, Serotonin, 5-HT1
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology*

Substances

  • 5-methyl-8-hydroxy-2-(di-n-propylamino)tetralin
  • Piperazines
  • Pyridines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin