Comparison of two alpha-noradrenergic agonists (clonidine and guanfacine) on norepinephrine turnover in the cortex of rats during morphine abstinence

European Journal of Pharmacology
J R ZigunR H Roth

Abstract

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.

References

Apr 29, 1978·Lancet·M S GoldH D Kleber
Aug 1, 1979·European Journal of Pharmacology·J N CrawleyR H Roth
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Citations

Oct 1, 1987·Pharmacology, Biochemistry, and Behavior·M S Kleven, S B Sparber
May 1, 1996·Drug and Alcohol Dependence·P J LittleC M Kuhn
May 20, 1998·Drug and Alcohol Dependence·A PinelliR Spezia
Jan 1, 1983·Journal of Neurochemistry·M P Galloway, R H Roth
May 1, 1985·Naunyn-Schmiedeberg's Archives of Pharmacology·J W van der Laan

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