A low dose of xylamine produces sustained and selective decreases in rat brain norepinephrine without evidence of neuronal degeneration.
The effects of a chronic partial depletion of rat cortical NE by a single dose of xylamine (20 mg/kg i.p.) on pre- and postsynaptic noradrenergic functionality were studied 4 hr, 14, 21 and 35 days after treatment. This dose of xylamine resulted in a 40 to 50% selective decrease in cortical levels of NE and the major metabolites of NE, 3,4-dihydroxyphenylethyleneglycol and 3-methoxy-4-hydroxyphenylethyleneglycol and, when measured after 35 days, [3H]desipramine binding and dopamine-beta-hydroxylase activity were at control levels, which would indicate that the NE nerve terminals in the cortex were intact. The 21- or 35-day deficit of NE did not affect alpha-1, alpha-2, beta, dopamine2, 5-hydroxytryptamine, or gamma-aminobutyric acidB receptor densities, or the beta receptor mediated adenylate cyclase activity. In addition, desipramine (10 mg/kg i.p.) administration for 14 days (days 20 through 34) was able to down-regulate beta receptor number (16% decrease) and reduce NE-stimulated adenylate cyclase activity (22% decrease), indicating that postsynaptic plasticity was still maintained. Affective disorders do not appear to be associated with a substantial (or readily measurable) decrease in brain NE concentrations and there is no consistent evidence of an altered beta receptor responsiveness. Thus, partial depletion of NE with xylamine might represent a biochemical model reflecting the involvement of NE in depression which could be used to investigate more sensitive markers of altered noradrenergic function.[1]References
- A low dose of xylamine produces sustained and selective decreases in rat brain norepinephrine without evidence of neuronal degeneration. Dudley, M.W., Siegel, B.W., Ogden, A.M., McCarty, D.R. J. Pharmacol. Exp. Ther. (1988) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
