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

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Abstract

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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Acknowledgements

This study has been supported by “Fondo de Investigación Sanitaria” (PI031430) and “Plan Andaluz de Investigación” (CTS-510).

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Authors and Affiliations

  1. Pharmacology and Neuroscience Research Group, Department of Neuroscience (Pharmacology and Psychiatry), School of Medicine, University of Cádiz, Plaza Falla 9, 11003, Cádiz, Spain

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

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  1. Esther Berrocoso
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  2. M. Olga Rojas-Corrales
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  3. Juan A. Mico
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Correspondence to Juan A. Mico.

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Berrocoso, E., Rojas-Corrales, M.O. & Mico, J.A. Differential role of 5-HT1A and 5-HT1B receptors on the antinociceptive and antidepressant effect of tramadol in mice. Psychopharmacology 188, 111–118 (2006). https://doi.org/10.1007/s00213-006-0464-6

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  • DOI: https://doi.org/10.1007/s00213-006-0464-6

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