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A) 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 Oxycodone Buprenorphine Rats like tramadol Tramadol plus pindolol Tramadol and analgesia Tramadol: pharmacology Tramadol as an antidepressant Tramadol: risk benefit analysis Tramadol versus buprenorphine Tramadol : morning or evening? Methadone for trama