Effects of serotonin receptor antagonists and agonists on the tail-flick response in mice involve altered tail-skin temperature.

Tail-flick latency and tail-skin temperature were measured in mice after administration of serotonin (5-HT) receptor antagonists (metergoline and metitepin) and agonists [5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)]. Metergoline (4 mg/kg) and metitepin (0.5 mg/kg) reduced the tail-flick latencies and increased the tail-skin temperatures, but the effect on the tail-flick latencies was non-significant when the effect of temperature was taken into account. Both 5-MeODMT (3 mg/kg) and 8-OH-DPAT (1 mg/kg) reduced the tail-skin temperature but only 5-MeODMT increased the tail-flick latencies. The effect of 5-MeODMT on tail-flick latencies was still highly significant when the effect of temperature was taken into account. The results show that the apparent hyperalgesia elicited by 5-HT receptor antagonists in the tail-flick test in the mouse is secondary to increased tail-skin temperature and not due to increased nociceptive sensitivity. The antinociceptive effect of 5-MeODMT in the tail-flick test can, however, not be explained by effects of temperature.