Stimulation of central serotonin turnover by beta-adrenoceptor agonists

The beta 2-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 beta 1-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 micrograms). Direct application of the compound into the dorsal raphe nucleus at doses of 100 ng and 1 microgram were without effect, and only minimal 5-HIAA increases occurred after the high dose of 10 micrograms. The effects of salbutamol on the concentrations of 5-HIAA were antagonized by both propranolol and WB4101, indicating an involvement not only of beta-receptors but also of postsynaptic alpha-receptors. The evidence for an against a central site of action of beta-agonists with respect to their effect on serotonergic systems is discussed.