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Differential role of 5-HT1A and 5-HT1B receptors on the antinociceptive and antidepressant effect of tramadol in mice (2006)

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Differential role of 5-HT1A and 5-HT1B receptors on the antinociceptive and antidepressant effect of tramadol in mice (2006)

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Psychopharmacology (2006) 188:111–118

Esther Berrocoso, M. Olga Rojas-Corrales
Juan A. Mico

RATIONALE: Tramadol, (1RS,2RS)-2-[(dimethylamine)-methyl]-1-(3-methoxyphenyl)-cyclohexanol hydrochloride, is an atypical analgesic which binds weakly to ì-opioid receptors and enhances the extra-neuronal concentration of noradrenaline and serotonin by interference with both the uptake and release mechanisms.

OBJECTIVES: The present study was undertaken to evaluate the potential role of 5-HT1A and 5-HT1B receptors on the analgesic and antidepressant-like effect of tramadol. METHODS: The effect of either a selective 5-HT1A receptor antagonist (WAY 100635; N-2-[4-(2-methoxyphenyl-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane carboxamide; 0.2-0.8, 8 mg/kg) or a selective 5-HT1B receptor antagonist (SB 216641; N-[3-(3-dimethylamino) ethoxy-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; 0.2-0.8, 8 mg/kg) was investigated in mice in combination with tramadol by means of the hot-plate test, a phasic nociceptive model, and the forced swimming test, a paradigm aimed at screening potential antidepressants.

RESULTS: The results showed that WAY 100635 enhanced the antinociceptive effect and produced a large decrease in the antidepressant-like effect of tramadol. In contrast, SB 216641 did not significantly modify either the analgesic or the antidepressant-like effects of tramadol.

CONCLUSIONS: These findings suggest that 5-HT1A receptors modulate the analgesic and the antidepressant-like effects of tramadol in differing ways. The results suggest the involvement of the 5-HT1A autoreceptors from the raphe nuclei and spinal 5-HT1A receptors in the antinociceptive effect. In contrast, the 5-HT1A receptors located in the forebrain may be responsible for the blockade of the antidepressant-like effect of tramadol. 5-HT1B receptors seem not to modify these effects in the models investigated.

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Submitted by Jatelka

23-02-2008
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Keywords: 5ht-1a serotonin tramadol 5ht-1b

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