Summary
The urinary excretion rates of noradrenaline and adrenaline — as an index of sympatho-adrenal activity — were assessed in a group of rats previously treated with the noradrenergic toxic agent DSP-4. The suppressive effects of clonidine (10μg/kg) on urinary NA excretion were also evaluated. Basal noradrenaline and adrenaline excretion rates were higher in DSP-4 treated rats than in controls. Clonidine elicited a marked suppression of urinary noradrenaline excretion rates in control rats but not in those treated with DSP-4 90–120 days before. Endogenous catecholamine level determinations, 120 days after DSP-4 administration, evidenced, on the one hand, an almost complete depletion of noradrenaline levels in spinal cord, cerebral cortex, and hippocampus. On the other hand, a significant increase of noradrenaline in the kidney and of adrenaline in the adrenal gland was found. These results are interpreted as indicating that the lesion of central noradrenergic pathways induces a sympatho-adrenal hyperactivity as well as an impaired response to alpha-2 adrenergic receptor agonists.
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References
Aghajanian G, Rogawski M (1983), The physiological role of alpha-adrenoreceptors in the CNS. Trends Pharmacol Sci 4: 315–317
Agharanya J, Wurtman R (1982) Studies on the mechanism by which tyrosine raises urinary catecholamines. Biochem Pharmacol 31: 3577–3580
Andén N, Grabowski M, Strombon V (1976) Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Archs Pharmacol 292: 43–52
Ball S, Gunn I, Douglas I (1982) Renal handling of dopa, dopamine, norepinephrine, and epinephrine in the dog. Am J Physiol 242: F 56-F 62
Barbeito L, Lista A, Silveira R, Dajas F (1984) Resting urinary catecholamine excretion in schizophrenics: methodology and interpretation of results. Biol Psychiat 19: 1419–1425
Bravo El (1983) Effect of clonidine on sympathetic function. Chest 83: 369–371
Charney D, Heninger G, Stemberg D, Hafstand K, Giddings S, Landes H (1982) Adrenergic receptor sensitivity in depression. Arch Gen Psychiat 39: 290–294
Dajas F, Lista A, Barbeito L (1984) High urinary norepinephrine excretion in major depressive disorders: effects of a new type of MAO inhibitor (moclobemide, Ro-11 1163). Acta Psychiat Scand 70: 432–437
Da Prada M (1980) Concentration, dynamics and functional meaning of catecholamines in plasma and urine. Trends Pharmacol Sci 1: 157–159
Dooley D, Mogilnicka E, Delini-Stula A, Waechter F, Truog A, Wood J (1983) Functional supersensitivity to adrenergic agonists in the rat after DSP-4, a selective noradrenergic neurotoxin. Psychopharmacology 81: 1–5
FitzGerald G, Dollery C (1979) Biochemical indices of sympathetic function in man. Trends Pharmacol Sci 1: 84–86
Frankenhaeuser M (1971) Behavior and circulating catecholamines. Brain Res 31: 241–262
Franz D, Madsen P, Peterson R, Sangdee C (1982) Functional roles of monoaminergic pathways to sympathetic preganglionic neuron. Clin Exp Hypertens 4: 543–562
Goldstein D (1983) Plasma catecholamines and essential hypertension: an analytical review. Hypertension 5: 331–335
Goldstein D, McCarty R, Polinsky R, Kopin I (1983) Relationship between plasma norepinephrine and sympathetic neural activity. Hypertension 5: 552–559
Guyenet P, Cabot J (1981) inhibition of sympathetic preganglionic neurons by catecholamines and clonidine: mediation by an alpha-adrenergic receptor. J Neurosci 1: 908–917
Jaim-Etcheverry G, Zieher L (1980) DSP-4: a novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 188: 513–523
Jonsson G, Hallman H, Ponzio F, Ross S (1981) DSP-4 N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine a useful denervation tool for central and peripheral noradrenaline neurons. Eur J Pharmacol 72: 173–188
Jonsson G, Sachs C (1976) Regional changes in3H-NA uptake and catecholamines synthetic and catabolic enzymes in rats following neonatal 6-OH-DA treatment. Med Biol 54: 286–297
Keller R, Oke A, Mefford I, Adams R (1976) Liquid chromatography analysis of catecholamines, routine assay for regional brain mapping. Life Sci 19: 995–999
Kobinger W (1978) Central alpha-adrenergic systems as targets for hypotensive drugs. Rev Physiol Biochem Pharmacol 81: 40–100
Kobinger W, Pichler L (1976) Centrally induced reduction in sympathetic tone, a postsynaptic alpha-adrenoreceptor stimulating action of imidazolines. J Pharmacol 40: 311–320
Koslow S, Maas J, Bowden C, Davis J, Hanin I, Javaid J (1983) CSF and urinary biogenic amines and metabolites in depression and mania. A controlled, univariate analysis. Arch Gen Psychiat 40: 999–1010
Langer S (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32: 337–362
Lappe R, Henry D, Willis L (1982) Contribution of renal sympathetic nerves to the urinary excretion of norepinephrine. Can J Physiol Pharmacol 60: 1067–1072
Leduc J (1981) Catecholamines production and release in exposure and acclimation to cold. Acta Physiol Scand [Suppl] 53: 183
Loewy A, Neil J (1981) The role of descending monoaminergic systems in the central control of blood pressure. Fed Proc 40: 2778–2785
Nygren L, Olson L (1976) On spinal noradrenaline receptor supersensitivity: Correlation between nerve terminal densities and flexor reflexes various times after intracisternal 6-hydroxydopamine. Brain Res 116: 455–470
Sangdee C, Franz D (1983) Evidence for inhibition of sympathetic preganglionic neurons by bulbospinal epinephrine pathways. Neurosci Lett 37: 167–173
Schmitt H (1977) The pharmacology of clonidine and related compounds. In: Gross F (ed) Antihypertensive agents. Springer, Berlin Heidelberg New York Tokyo, pp 299–378
Silva P, Landsberg L, Besarab A (1979) Excretion and metabolism of catecholamines by the isolated perfused rat kidney. J Clin Invest 64: 850–857
Spector S, Tarver J, Berkowitz B (1972) Effects of drugs and physiological factors in the disposition of catecholamines in blood vessels. Pharmacol Rev 24: 191–202
Stephenson R, Sole M, Baines A (1982) Neural and extraneural catecholamine production by rat kidneys. Am J Physiol 242: F 261-F 266
Westlund K, Bowker R, Ziegler M, Coulter J (1983) Noradrenergic projections to the spinal cord of the rat. Brain Res 263: 15–31
Willis L, Lappe R, Henry D, Evan A, Terzian A (1980) Urinary excretion of radiolabelled norepinephrine after release from renal sympathetic nerves. Life Sci 27: 2541–2546
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Barbeito, L., Fernández, C., Silveira, R. et al. Evidences of a sympatho-adrenal dysfunction after lesion of the central noradrenergic pathways in rats. J. Neural Transmission 67, 205–214 (1986). https://doi.org/10.1007/BF01243348
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DOI: https://doi.org/10.1007/BF01243348