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Antidepressant-Like Effect of tramadol and its Enantiomers in Reserpinized Mice: Comparativestudy with Desipramine, Fluvoxamine, Venlafaxine and Opiates

Esther Berrocoso

Juan Gibert-Rahola

Pharmacology and Neuroscience Research Group, Department of Neuroscience, Faculty of Medicine, University of Cádiz, Cádiz, Spain

Juan Antonio Micó

Pharmacology and Neuroscience Research Group, Department of Neuroscience, Faculty of Medicine, University of Cádiz, Cádiz, Spainjuanantonio.mico{at}uca.es

Tramadol is a centrally acting analgesic that demonstrates opioid and monoaminergic properties. Several studies have suggested that tramadol could play a role in mood improvement. Moreover, it has previously been shown that tramadol is effective in the forced swimming test in mice and the learned helplessness model in rats, two behavioural modelspredictive of antidepressant activity. The aim of the present study was to test tramadol and its enantiomers in the reserpine test in mice, aclassical observational test widely used in the screening of antidepressant drugs. This test is a non-behavioural method where only objective parameters such as rectal temperature and palprebral ptosis are considered. Moreover, we compared the effects of tramadol and itsenantiomers with those of antidepressants (desipramine, fluvoxamine and venlafaxine) and opiates [morphine (–)-methadone and levorphanol]. Racemic tramadol, (–)-tramadol, desipramine and venlafaxine reversed the reserpine syndrome (rectal temperature and ptosis), whereas(+)-tramadol and fluvoxamine only antagonized the reserpine-induced ptosis, without any effect on temperature. Opiates did not reversereserpine-induced hypothermia. (–)-Methadone showed slight effects regarding reserpine-induced ptosis, morphine and levorphanol had no effect. These results show that tramadol has an effect comparable to clinically effective antidepressants in a test predictive of antidepressant activity, without behavioural implications. Together with other clinical and experimental data, this suggests that tramadol has an inherent antidepressant-like (mood improving) activity, and that this effect could have clinical repercussions on the affective component of pain.

Key Words: desipramine • fluvoxamine • levorphanol • methadone • morphine • reserpine test • tramadol • venlafaxine

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