Differential role of 5-HT(1A) and 5-HT (1B) receptors on the antinociceptive and antidepressant effect of tramadol in mice
Berrocoso E, Rojas-Corrales MO, Mico JA.
Pharmacology and Neuroscience Research Group,
Department of Neuroscience (Pharmacology and Psychiatry),
School of Medicine,
University of Cadiz, Plaza Falla 9, 11003, Cadiz, Spain,
Psychopharmacology (Berl). 2006 Sep;188(1):111-8.
ABSTRACTRATIONALE: Tramadol, (1RS,2RS)-2-[(dimethylamine)-methyl]-1-(3-methoxyphenyl)-cyclohexanol hydrochloride, is an atypical analgesic which binds weakly to i-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-HT(1A) and 5-HT(1B) receptors on the analgesic and antidepressant-like effect of tramadol. METHODS: The effect of either a selective 5-HT(1A) 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-HT(1B) 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-HT(1A) receptors modulate the analgesic and the antidepressant-like effects of tramadol in differing ways. The results suggest the involvement of the 5-HT(1A) autoreceptors from the raphe nuclei and spinal 5-HT(1A) receptors in the antinociceptive effect. In contrast, the 5-HT(1A) receptors located in the forebrain may be responsible for the blockade of the antidepressant-like effect of tramadol. 5-HT(1B) receptors seem not to modify these effects in the models investigated.Allodynia
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