title: Tramadol increases extracellular levels of serotonin and noradrenaline as measured by in vivo microdialysis in the ventral hippocampus of freely-moving rats.
abstract: Tramadol is an atypical opioid with monoamine re-uptake inhibition properties. The aim of the current study was to compare, using in vivo microdialysis, the effect of tramadol on extracellular serotonin (5-HT) and noradrenaline (NA) levels in the rat ventral hippocampus with the effects of the dual 5-HT/NA inhibitors (SNRIs) duloxetine and venlafaxine, the tricyclic antidepressant clomipramine, the selective 5-HT re-uptake inhibitor (SSRI) citalopram, and the selective NA re-uptake inhibitor (NRI) reboxetine. It was found that tramadol, duloxetine and venlafaxine increased extracellular levels of both, 5-HT and NA, in a dose-dependent manner. Clomipramine also increased extracellular 5-HT and NA levels, however not dose-dependently in the tested dose range. Citalopram selectively increased extracellular 5-HT levels. Reboxetine increased extracellular NA levels and also to a minimal degree 5-HT levels. It can be concluded that, albeit less efficacious, the effects of tramadol on serotonergic and noradrenergic neurotransmission resemble those of the dual 5-HT and NA re-uptake inhibitors duloxetine, venlafaxine, and clomipramine, and are different from those of the SSRI citalopram and the NRI reboxetine.
authors.affiliation: Grünenthal GmbH, Global Preclinical Research and Development, 52099 Aachen, Germany. Petra.Bloms-Funke@grunenthal.com
authors.forename: P
authors.initials: P
authors.lastname: Bloms-Funke
authors.forename: E
authors.initials: E
authors.lastname: Dremencov
authors.forename: T I F H
authors.initials: TI
authors.lastname: Cremers
authors.forename: T M
authors.initials: TM
authors.lastname: Tzschentke
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009294:Narcotics / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors; D014147:Tramadol / Q000494:pharmacology*; D014851:Wakefulness
chemical_list: D009294:Narcotics; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014147:Tramadol