Differential effects of activation of lumbar and thoracic 5-HT2A/2C receptors on nociception in rats.

The role of 5-HT2 receptors in nociceptive behaviour of rats was investigated using spinal administration of the 5-HT2A/2C receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI), the 5-HT2A/2C antagonist ketanserin and the glutamate receptor agonist NMDA. Nociceptive behaviour was scored after injections at upper thoracic or lumbosacral levels. DOI (0.1-10 mM, 15 microl) administered at the upper thoracic level induced pain-like behaviour in a dose-dependent manner and a long-lasting motor depression at the greatest dose. At the lumbosacral level a similar dose-dependent pain-like behaviour was observed, but it was less pronounced. Motor depression was not observed at any dose. Ketanserin injected before DOI blocked both nociceptive and motor effects. Stimulation of both NMDA and 5-HT2A/2C receptors had a mutually potentiating effect. The present results show that the effects of DOI were more pronounced at the upper thoracic than at the lumbosacral level. This is possibly caused by the difference in 5-HT2A/2C receptor density at the two levels. The motor depression induced by the greatest dose of DOI given at the upper thoracic level appears to mask the pain-like behaviour. The nociceptive behaviour seen after DOI injection is further increased following co-injection of NMDA.