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.
BACKGROUND
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.


OBJECTIVE
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.
Yalcin
Ipek
I
INSERM U-930 FRE CNRS 2448, Faculté des Sciences et Techniques, Université François Rabelais, Parc Grandmont, 37200 Tours, France. yalcinipek2003@yahoo.com
Coubard
Stéphanie
S
Bodard
Sylvie
S
Chalon
Sylvie
S
Belzung
Catherine
C
D015116:5,7-Dihydroxytryptamine; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013315:Stress, Psychological / Q000503:physiopathology; D014147:Tramadol / Q000494:pharmacology*
D000928:Antidepressive Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D014147:Tramadol