title: Chronic clonidine treatment produces desensitisation of post- but not presynaptic alpha 2-adrenoceptors.
abstract: Rats were treated chronically with clonidine by osmotic minipump (500 micrograms/kg daily for 14 days). One day after the end of the infusion period, the animals were pithed, and alpha 2-presynaptic and -postsynaptic adrenoceptor responses evaluated using inhibition of cardioaccelerator response to sympathetic stimulation by guanabenz, and pressor response to guanabenz respectively. Chronic clonidine treatment had no effect on the presynaptic effect of guanabenz, but the postsynaptic response to this agonist was decreased. In a separate group of pithed rats treated chronically with clonidine, there was no alteration in the increment in plasma noradrenaline concentration produced by sympathetic stimulation, and no alteration in the yohimbine-induced enhancement of plasma noradrenaline response to sympathetic stimulation. These data argue against desensitisation of peripheral presynaptic alpha 2-adrenoceptors by chronic administration of alpha 2-adrenoceptor agonist. Sympathetic hyperactivity following withdrawal of chronic clonidine treatment may be mediated by down-regulation of postsynaptic alpha 2-adrenoceptors in the CNS.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003000:Clonidine / Q000494:pharmacology*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006143:Guanabenz / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*
chemical_list: D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D006143:Guanabenz; D003000:Clonidine