Stimulation of central serotonin turnover by ?-adrenoceptor agonists

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Abstract
The β2-stimulators salbutamol (0.3–30 mg/kg i.v.) and clenbuterol (0.3 and 1 mg/kg i.v.), and, to a lesser extent, the β1-stimulators dobutamine (30 mg/kg i.v.) and prenalterol (30 mg/kg i.v.) increased serotonin metabolism in several rat brain areas, as indicated by increased concentrations of 5-hydroxyindoleacetic acid (5-HIAA) or increased tryptophan hydroxylation in vivo. With salbutamol, increases in 5-HIAA in c. striatum and brainstem, but not in cortex, were observed after intraventricular administration of relatively low doses (3–30 μg). Direct application of the compound into the dorsal raphe nucleus at doses of 100 ng and 1 μg were without effect, and only mininal 5-HIAA increases occurred after the high dose of 10 μg. The effects of salbutamol on the concentrations of 5-HIAA were antagonized by both propranolol and WB4101, indicating an involvement not only of β-receptors but also of postsynaptic α-receptors. The evidence for and against a central site of action of β-agonists with respect to their effect on serotonergic systems is discussed.

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