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Effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus on the antidepressant-like action of tramadol in the unpredictable chronic mild stress in mice

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Abstract

Rationale

Tramadol is a centrally acting clinically effective analgesic, with a weak opioid receptor affinity. It shows antidepressant-like effects in animal models such as forced swimming test, learned helplessness, and unpredictable chronic mild stress (UCMS) and enhances the concentrations of noradrenaline (NA) and serotonin (5-HT) by interfering with their reuptake and release mechanisms, like some antidepressants.

Objectives

The aim of this study was to explore whether the antidepressant-like effects of tramadol is affected by the serotonergic system. For this purpose, the effects of a lesion of the dorsal raphe nucleus (DRN) by 5,7-dihydroxytryptamine (5,7-DHT) on the action of tramadol (20 mg/kg, i.p.) on depression-related behavior and neurochemical correlates were investigated in mice. From the third week onward, we administered tramadol chronically during 4 weeks.

Results

Tramadol reversed the physical and behavioral abnormalities induced by the UCMS. Furthermore, the lesion of the DRN by 5,7-DHT antagonized the antidepressant-like effects of tramadol on the coat state, in the splash test but not in the resident-intruder test. The results obtained by high-pressure liquid chromatography showed that the level of 5-HT was reduced by the lesion in some brain regions without affecting the level of NA. Moreover, while the UCMS regimen diminished the level of 5-HT, tramadol increased the level of this neurotransmitter in certain regions.

Conclusions

These results seem to indicate that the serotonergic system is critically involved in the antidepressant-like effects of tramadol in the UCMS in mice.

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Author notes

  1. Stéphanie Coubard

    Present address: Institut de Médecine Aérospatiale du Service de Santé des Armées, Base 217, B.P.73, 91223, Brétigny-sur Orge Cedex, France

Authors and Affiliations

  1. INSERM U-930 FRE CNRS 2448, Faculté des Sciences et Techniques, Université François Rabelais, Parc Grandmont, 37200, Tours, France

    Ipek Yalcin, Stéphanie Coubard & Catherine Belzung

  2. Department of Pharmacology, Faculty of Medicine, Cukurova University, 01330, Balcali, Adana, Turkey

    Ipek Yalcin

  3. INSERM U619, Laboratoire de Biophysique médicale et pharmaceutique, Université François Rabelais, Parc Grandmont, 37200, Tours, France

    Sylvie Bodard & Sylvie Chalon

Authors
  1. Ipek Yalcin
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  2. Stéphanie Coubard
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  3. Sylvie Bodard
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  4. Sylvie Chalon
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  5. Catherine Belzung
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Correspondence to Ipek Yalcin.

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This research was conducted in accordance with the European Community guidelines for the use of experimental animals.

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Yalcin, I., Coubard, S., Bodard, S. et al. Effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus on the antidepressant-like action of tramadol in the unpredictable chronic mild stress in mice. Psychopharmacology 200, 497–507 (2008). https://doi.org/10.1007/s00213-008-1227-3

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  • DOI: https://doi.org/10.1007/s00213-008-1227-3

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