Comparison of two alpha-noradrenergic agonists (clonidine and guanfacine) on norepinephrine turnover in the cortex of rats during morphine abstinence.
The effects of the alpha-agonists clonidine and guanfacine on rat cortical norepinephrine turnover during morphine withdrawal were assessed. Cortical norepinephrine levels were measured, after administration of alpha-methyl-p-tyrosine, by fluorometric assay. Chronic treatment with morphine did not affect norepinephrine levels or norepinephrine turnover. In control animals, doses up to 200 micrograms/kg clonidine and 1060 micrograms/kg guanfacine did not affect norepinephrine steady state levels, but did reduce alpha-methyl-p-tyrosine-induced norepinephrine depletion. As little as 5 micrograms/kg clonidine reversed the accelerated turnover observed during naloxone precipitated morphine withdrawal; while for guanfacine, the minimum effective dose was 212 micrograms/kg. the ED50 for guanfacine's reversal of the withdrawal-induced acceleration of turnover was approximately 60 times that for clonidine.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008781:Methyltyrosines / Q000494:pharmacology; D009021:Morphine Dependence / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010648:Phenylacetates / Q000494:pharmacology; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D006146:Guanidines; D008781:Methyltyrosines; D010648:Phenylacetates; D016316:Guanfacine; D003000:Clonidine; D009638:Norepinephrine