Journal
PSYCHOPHARMACOLOGY
Volume 200, Issue 4, Pages 497-507Publisher
SPRINGER
DOI: 10.1007/s00213-008-1227-3
Keywords
5,7-dihydroxytryptamine; desipramine; dorsal raphe nucleus; tramadol; unpredictable chronic mild stress; mice
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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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