Effects of 5-HT receptor agonists and antagonists on a reflex response to radiant heat in normal and spinally transected rats.

Tail-flick latency (TFL) was tested in intact and spinally transected rats. Spinal transection permanently lowered the TFL by 25-30%. A diurnal rhythm in nociception was found in intact but not in spinal rats with maximum sensitivity during the early light period. Administration of the 5-hydroxytryptamine (5-HT) receptor antagonists metergoline (0.06-2.0 mg/kg), mianserin (1.0 and 5.0 mg/kg) or methiothepin (0.1-2.5 mg/kg) reduced the TFL of normal rats to the same level as that of the transected animals. The diurnal variation in TFL was also abolished by metergoline. Neither drug changed the TFL of the transected rats. The 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 0.5-2.0 mg/kg) induced the 5-HT syndrome in intact rats and elicited spinal reflexes in the transected animals. Concomitantly, the TFLs of both groups were elevated to the same maximum level, approximately 25% above normal TFL of intact rats. Transected rats consistently responded to lower doses than intact rats, indicating 5-HT receptor supersensitivity. The 5-MeODMT effects were reversed by administration of 5-HT antagonists. Administration of the 5-HT precursor dl-5-hydroxytryptophan (200 mg/kg), after inhibition of peripheral decarboxylation by carbidopa (75 mg/kg), also elevated the TFL and induced other behavioral signs of 5-HT stimulation. It is concluded tht there exists a tonic inhibitory influence with diurnal variations on spinal nociceptive reflexes in the rat. The data reported suggest that this inhibition is mediated by descending 5-HT pathways.