Changes in central serotoninergic transmission affect clonidine analgesia in monkeys.
The effects of changes in central serotoninergic transmission on clonidine analgesia were assessed in monkeys. The minimum electrical current required for producing jaw opening is referred to as the pain threshold. Pain was induced by electrical stimulation of tooth pulp afferents. In the first series of studies, intracerebroventricular administration of clonidine (5-30 micrograms) produced dose-dependent analgesia in monkeys. The clonidine-induced analgesia was abolished or attenuated by prior injection of the animals with p-chlorophenylalanine or 5,7-dihydroxytryptamine into the third cerebral ventricle. On the other hand, pretreatment of the animals by injecting 5-HT or its precursor 5-hydroxytryptophan into the cerebral ventricle potentiated the clonidine-induced analgesia in monkeys. In the second series of experiments, administration of clonidine (1-10 micrograms) into the diencephalic periventricular gray (of the anterior hypothalamic portion), the periaqueductal gray, or the dorsal raphe nuclei also produced dose-dependent analgesia in monkeys. The analgesia induced by clonidine injection into the diencephalic periventricular gray or the periaqueductal gray was effectively antagonized by pretreatment of the animals by injecting two 5-HT receptor antagonists (such as ketanserine and methysergide) into the diencephalic periventricular gray or the periaqueductal gray. The clonidine-induced analgesia in monkeys was not affected by pretreatment of the animals with injections of either ketanserine or methysergide into the dorsal raphe nuclei. The results suggest that the functional activity of central 5-HT neurons correlate well with the analgesic sensitivity of clonidine microinjected centrally. In addition, the analgesia induced by clonidine microinjected into the diencephalic periventricular gray or the periaqueductal gray was mediated by the 5-HT receptors at the site of injection.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology; D007276:Injections, Intraventricular; D007650:Ketanserin / Q000494:pharmacology; D008251:Macaca; D008297:Male; D008845:Microinjections; D009619:Nociceptors / Q000187:drug effects; D010487:Periaqueductal Gray; D011903:Raphe Nuclei; D012701:Serotonin / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D000700:Analgesics; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D007650:Ketanserin; D006916:5-Hydroxytryptophan; D003000:Clonidine; D010134:Fenclonine