Tramadol increases extracellular levels of serotonin and noradrenaline as measured by in vivo microdialysis in the ventral hippocampus of freely-moving rats.

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.