Format

Send to

Choose Destination
Neuroscience. 2009 Aug 18;162(2):444-52. doi: 10.1016/j.neuroscience.2009.04.072. Epub 2009 May 5.

Role of peripheral and spinal 5-HT6 receptors according to the rat formalin test.

Author information

1
Departamento de Farmacobiología, Cinvestav, Sede Sur, Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330 México, DF, Mexico.

Abstract

The present study assessed the possible pronociceptive role of peripheral and spinal 5-HT(6) receptors in the formalin test. For this, local peripheral administration of selective 5-HT(6) receptor antagonists N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)-benzenesulphonamide (SB-399885) (0.01-1 nmol/paw) and 4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzene-sulfonamide hydrochloride (SB-258585) (0.001-0.1 nmol/paw) significantly reduced formalin-induced flinching. Local peripheral serotonin (5-HT) (10-100 nmol/paw) or 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole hydrochloride (EMD-386088) (0.01-0.1 nmol/paw; a selective 5-HT(6) receptor agonist) augmented 0.5% formalin-induced nociceptive behavior. The local pronociceptive effect of 5-HT (100 nmol/paw) or EMD-386088 (0.1 nmol/paw) was significantly reduced by SB-399885 or SB-258585 (0.1 nmol/paw). In contrast to peripheral administration, intrathecal injection of 5-HT(6) receptor antagonists SB-399885 and SB-258585 (0.1-10 nmol/rat) did not modify 1% formalin-induced nociceptive behavior. Spinal 5-HT (50-200 nmol/rat) significantly reduced formalin-induced flinching behavior during phases 1 and 2. Contrariwise, intrathecal EMD-386088 (0.1-10 nmol/rat) dose-dependently increased flinching during phase 2. The spinal pronociceptive effect of EMD-386088 (1 nmol/rat) was reduced by SB-399885 (1 nmol/rat) and SB-258585 (0.1 nmol/rat). Our results suggest that 5-HT(6) receptors play a pronociceptive role in peripheral as well as spinal sites in the rat formalin test. Thus, 5-HT(6) receptors could be a target to develop analgesic drugs.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center