Tramadol induces antidepressant-type effects in mice.
Tramadol is a clinically-effective, centrally-acting analgesic. This drug is a racemic mixture of two enantiomers, each one displaying different mechanisms: (+)tramadol displays opioid agonist properties and inhibits serotonin reuptake while (-)tramadol inhibit preferentially noradrenaline reuptake. The action of tramadol on the monoaminergic reuptake is similar to that of antidepressant drugs. Therefore, we have examined the effects of (+/-)tramadol, (+)tramadol and (-)tramadol in a test predictive of antidepressant activity, the forced swimming test in mice. Both (+/-)tramadol and its (-) enantiomer displayed a dose-dependent reduction on immobility; while the effect induced by the (+) enantiomer was not significant. Inhibition of noradrenaline synthesis, but not of serotonin synthesis, was capable of blocking the effect of (+/-)tramadol. The alpha-adrenoceptor antagonist phentolamine, as well as the alpha2-adrenergic antagonist yohimbine, and the beta-adrenoceptor blocker propranolol countered the immobility-reducing action of (+/-)tramadol. Moreover, neither the serotoninergic blocker methysergide nor the opioid antagonist naloxone antagonized the effect of (+/-)tramadol. Our results show that (+/-)tramadol and (-)tramadol have antidepressant-like effect in mice, probably mediated by the noradrenergic system rather than the serotoninergic or opioidergic ones.
Rojas-Corrales
M O
MO
Department of Neuroscience, Faculty of Medicine, University of Cádiz, Spain.
Gibert-Rahola
J
J
Micó
J A
JA
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D009638:Norepinephrine / Q000096:biosynthesis / Q000502:physiology; D012701:Serotonin / Q000096:biosynthesis / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013550:Swimming; D014147:Tramadol / Q000494:pharmacology*
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D009294:Narcotics; D012702:Serotonin Antagonists; D012701:Serotonin; D014147:Tramadol; D007099:Imipramine; D009638:Norepinephrine