Effects of clonidine on the rate of noradrenaline turnover in discrete areas of the rat central nervous system.
Turnover of noradrenaline in various regions of the rat brain was estimated by the decrease in noradrenaline content and/or formaldehyde-induced catecholamine fluorescence after inhibition of noradrenaline biosynthesis with alpha-methyl-p-tyrosine. Clonidine (0.1 and 0.3 mg/kg p.o.) decelerated the decrease in noradrenaline content of the locus coeruleus, the nucleus of the solitary tract, the intermediolateral cell column and the ventral horn of the thoracic spinal cord, as measured in tissue punches of the respective regions with a sensitive radioenzymatic method. In all these central regions the clonidine-induced decrease in noradrenaline turnover was antagonized by yohimbine, but not by phenoxybenzamine, indicating mediation through central alpha 2-adrenoceptors, similar to the cardiovascular effects of clonidine. When given alone, both yohimbine and phenoxybenzamine accelerated the disappearance of noradrenaline after inhibition of its biosynthesis. The combined results of radioenzymatic assay and fluorescence histochemistry determinations demonstrated that clonidine markedly reduced noradrenaline turnover in central noradrenaline-containing nerve terminals, but had no effect on the cell bodies of the A1 and A2 cell groups. Noradrenaline turnover was, however, decreased in projection areas of the A1 and A2 cell groups, namely the intermediolateral cell column of the spinal cord and nucleus of the solitary tract, respectively. This observation argues against the existence of a neuronal feedback loop running from the projection areas to the cell bodies of the A1 and A2 cell groups and mediating inhibition of noradrenaline turnover. The effect of clonidine on noradrenaline turnover is, therefore, most likely the result of a local feedback inhibition through presynaptic alpha-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D006651:Histocytochemistry; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D008781:Methyltyrosines; D010643:Phenoxybenzamine; D015016:Yohimbine; D019805:alpha-Methyltyrosine; D003000:Clonidine; D009638:Norepinephrine