CNS Disorders Division, Wyeth-Ayerst Research, Princeton, NJ 08543-8000, USA. dawsonl@war.wyeth.com
European journal of pharmacology 1998 Mar 12Clinical studies in which serotonin specific reuptake inhibitors have been co-administered with pindolol have demonstrated a shortened time to onset of antidepressant activity. This effect has been attributed to the antagonist effects of pindolol at the presynaptic 5-HT1A receptor which augments the action of the serotonin specific reuptake inhibitors. In the present study, we demonstrate that acute fluoxetine-induced increases in extracellular serotonin concentrations, as measured by microdialysis in the frontal cortex, can be potentiated by 5-HT1A receptor blockade using N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(pyridinyl)cyclohexa necarboxamide (WAY100635), the silent and selective 5-HT1A receptor antagonist. WAY100635 at doses as low as 0.03 mg/kg s.c. maintained this potentiation effect across a range of fluoxetine doses. In addition, using antagonists with different intrinsic agonist activities for the 5-HT1A receptor, we have determined that only compounds with very low intrinsic agonist activity can produce a potentiation of the acute fluoxetine-induced increases in extracellular serotonin.
L A Dawson, H Q Nguyen. Effects of 5-HT1A receptor antagonists on fluoxetine-induced changes in extracellular serotonin concentrations in rat frontal cortex. European journal of pharmacology. 1998 Mar 12;345(1):41-6
PMID: 9593592
View Full Text