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Tramadol induces antidepressant-type effects in mice
M O Rojas-Corrales1, J Gibert-Rahola, J A Micó
1Department of Neuroscience, Faculty of Medicine, University of Cádiz, Spain.
Life Sciences
|September 28, 1998
Summary
Tramadol and its (-) enantiomer show antidepressant-like effects in mice, primarily through the noradrenergic system. This suggests a potential role for tramadol in managing depression, distinct from its opioid and serotonergic actions.
Area of Science:
- Pharmacology
- Neuroscience
- Psychiatry
Background:
- Tramadol is a centrally-acting analgesic and a racemic mixture of two enantiomers.
- The enantiomers, (+)tramadol and (-)tramadol, exhibit distinct mechanisms: opioid agonism and serotonin reuptake inhibition for (+), and noradrenaline reuptake inhibition for (-).
- Tramadol's monoaminergic reuptake inhibition resembles antidepressant drug action.
Purpose of the Study:
- To investigate the antidepressant-like activity of racemic tramadol ((+/-)tramadol), (+)tramadol, and (-)tramadol.
- To elucidate the neurochemical pathways (serotonergic, noradrenergic, opioidergic) involved in tramadol's potential antidepressant effects.
- To assess the role of noradrenaline and serotonin synthesis inhibition on tramadol's efficacy.
Main Methods:
- Utilized the forced swimming test in mice, a standard model for predicting antidepressant activity.
- Administered varying doses of (+/-)tramadol, (+)tramadol, and (-)tramadol.
- Investigated the effects of inhibiting noradrenaline and serotonin synthesis on tramadol's action.
- Examined the influence of adrenergic (alpha and beta) and serotonergic antagonists, as well as opioid antagonists, on tramadol's immobility-reducing effects.
Main Results:
- Both (+/-)tramadol and (-)tramadol significantly reduced immobility time in a dose-dependent manner.
- (+)tramadol did not produce a significant antidepressant-like effect.
- Inhibition of noradrenaline synthesis blocked the effect of (+/-)tramadol, while serotonin synthesis inhibition did not.
- Adrenergic antagonists (phentolamine, yohimbine, propranolol) antagonized the immobility-reducing action of (+/-)tramadol.
- Serotonergic (methysergide) and opioid (naloxone) antagonists did not affect tramadol's action.
Conclusions:
- Tramadol and its (-) enantiomer possess antidepressant-like effects in mice.
- The antidepressant-like activity of tramadol appears to be primarily mediated by the noradrenergic system.
- The serotonergic and opioidergic systems are less likely to be involved in tramadol's antidepressant-like effects.