title: (-)-Pindolol, but not buspirone, potentiates the citalopram-induced rise in extracellular 5-hydroxytryptamine.
abstract: Recent open clinical studies suggest that pindolol and buspirone may enhance the efficacy and/or shorten the latency to antidepressant action of selective serotonin reuptake inhibitors (SSRI) in unipolar major depressive disorder. The present investigation addressed the possibility that these agents share the ability to enhance the extracellular 5-hydroxytryptamine (5-HT)-elevating response to the SSRI citalopram. For the purpose, in vivo microdialysis in the rat ventral hippocampus was employed. (-)-Pindolol (8 mg/kg s.c.) augmented the citalopram (5 mg/kg s.c.)-induced rise of extracellular 5-HT levels, whereas buspirone (5 mg/kg s.c.) failed to do so. This effect of (-)-pindolol probably reflects its ability to block 5-HT1A autoreceptors, thereby abating the citalopram-induced indirect activation of these sites (secondary to the inhibition of 5-HT reuptake and elevation of extracellular 5-HT in the midbrain raphe). The lack of effect of buspirone in this model indicates that the clinically observed antidepressant augmentation action of buspirone is not mediated indirectly, via enhanced extracellular levels of 5-HT.
authors.affiliation: Department of Pharmacology, University of Göteborg, Sweden. stephan.hjorth@pharm.gu.se
authors.forename: S
authors.initials: S
authors.lastname: Hjorth
mesh_terms: D000818:Animals; D002065:Buspirone / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology*; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010869:Pindolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D002065:Buspirone; D015283:Citalopram; D010869:Pindolol; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors