Enhancement of clonidine-induced analgesia by lesions induced with spinal and intracerebroventricular administration of 5,7-dihydroxytryptamine.

The role of serotonin (5-HT) in analgesia induced by clonidine was examined by determining the effect of intraspinal (i.s.) and intracerebroventricular (i.c.v.) injections of 5,7-dihydroxytryptamine (5,7-DHT) on analgesia produced by clonidine in the tail-flick and hot plate tests. Depletion of amines was verified by high performance liquid chromatography analysis. Intraspinal injections of 5,7-DHT potentiated the action of clonidine in both tests for analgesia and caused depletion of 5-HT in the spinal cord. Intracerebroventricularly injected 5,7-DHT also increased the action of clonidine and depleted 5-HT in brain as well as in the spinal cord. In the groups given intracerebroventricular injections, there appeared to be a biphasic increase in the action of the clonidine. Significant hyperalgesia from pretreatment with neurotoxin was observed only on a limited number of occasions. The present results indicate that 5-HT mechanisms in the CNS are important mediators of the analgesic action of clonidine. Interactions between clonidine and 5-HT systems at both spinal and supraspinal sites are considered.