Effect of repeated administration of clenbuterol on the regulation of beta-adrenoceptors in the central nervous system of the rat.

A. Frazer, G. Ordway, J. O'Donnell, P. Vos, B. Wolfe

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Abstract

The effect of the centrally acting beta-adrenoceptor agonist clenbuterol on beta-adrenergic responsiveness, beta-receptor density and N-protein coupling was studied in the rat cerebral cortex (which contains primarily beta 1-receptors) and cerebellum (containing mostly beta 2-receptors). The objective was to determine whether clenbuterol's effect on these variables was similar to that produced by standard antidepressants. When given to rats repeatedly, clenbuterol caused a decrease in beta-adrenergic responsiveness in slices from either the cerebral cortex or the cerebellum. The decreased beta-responsiveness in the cerebellum was associated with a decrease both in the density of beta-receptors and in receptor/N-protein coupling. In the cortex, only reduced receptor/N-protein coupling was observed by in vitro ligand-binding methods. However, when quantitative autoradiography was employed, clenbuterol treatment was found to reduce the binding of [125I]iodopindolol to beta 2-receptors throughout the brain, whereas binding to beta 1-receptors was not reduced. The down-regulation of beta 2-receptors by clenbuterol is due to its acting centrally as a beta 2-agonist. Although clenbuterol has about an equal affinity for beta 1-receptors and beta 2-receptors, no evidence was found for agonist activity of this drug at beta 1-receptors in the cerebral cortex. The strategies described here should be helpful in investigating important properties of centrally acting beta-agonists that might have potential as antidepressants.

Original languageEnglish (US)
Pages (from-to)170-190
Number of pages21
JournalCiba Foundation symposium
Volume123
StatePublished - 1986
Externally publishedYes

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