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 inves tigated 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 behavi our was scored after injections at upper thoracic or lumbosacral level s. DOI (0.1-10 mM, 15 mu l) administered at the upper thoracic level i nduced pain-like behaviour in a dose-dependent manner and a long-lasti ng motor depression at the greatest dose. At the lumbosacral level a s imilar dose-dependent pain-like behaviour was observed, but it was les s pronounced. Motor depression was not observed at any dose. Ketanseri n injected before DOI blocked both nociceptive and motor effects. Stim ulation of both NMDA and 5-HT2A/2C receptors had a mutually potentiati ng effect. The present results show that the effects of DOI were more pronounced at the upper thoracic than at the lumbosacral level. This i s possibly caused by the difference in 5-HT2A/2C receptor density at t he two levels. The motor depression induced by the greatest dose of DO I given at the upper thoracic level appears to mask the pain-like beha viour. The nociceptive behaviour seen after DOI injection is further i ncreased following co-injection of NMDA. Copyright (C) 1997 Elsevier S cience Inc.