Brain research
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This study was designed to evaluate the role of spinal glutamatergic receptors in the antinociception elicited by agmatine in mice. Intraperitoneal (i.p.) administration of agmatine (1.0-100.0 mg/kg) dose dependently inhibited the nociceptive response induced by intrathecal (i.t.) injection of glutamate, N-methy-D-aspartate (NMDA) and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), with mean ID(50) values of 16.7, 6.8 and 27.0 mg/kg, respectively. However, agmatine completely failed to affect the nociception induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainic acid (kainate). ⋯ At a high dose, MK-801 (0.5 mg/kg, i.p.) significantly inhibited the biting response induced by i.t. administration of all the glutamatergic agonists tested: glutamate, AMPA, NMDA, kainate and trans-ACPD, with inhibitions of 49 +/- 8, 84 +/- 16, 84 +/- 3, 76 +/- 8 and 97 +/- 2%, respectively. Together, these results provide experimental evidence indicating that agmatine given systemically and spinally produce marked antinociception at spinal sites in mice. Furthermore, an interaction with glutamate receptors, namely NMDA and trans-ACPD, metabotropic and NMDA-ionotropic origin, by a mechanism similar to that of nitric oxide (NO) inhibitors, seems to account for the agmatine antinociceptive action.