Increased brain serotonergic and noradrenergic activity after repeated systemic administration of the beta-2 adrenoceptor agonist salbutamol, a putative antidepressant drug

Abstract

Subchronic (5 mg/kg SC, twice daily for 14 days) but not acute administration of the beta-2-adrenoceptor agonist salbutamol to rats caused a significant increase in the accumulation of 5-hydroxytryptophan in the limbic forebrain, the corpus striatum and the cerebral cortex when measured during 30 min after inhibition of L-amino acid decarboxylase by NSD 1015 (100 mg/kg IP). Simultaneously assayed tryptophan concentrations in the same brain regions were not affected. These results indicate an increase in the in vivo rate of tryptophan hydroxylation in the brain, produced by subchronic salbutamol administration. The effect of salbutamol treatment on brain catecholamine(CA) utilization was estimated by studying the disappearance of CA in the brain after inhibition of tyrosine hydroxylase by alpha-methyltyrosine methyl ester (H 44/68), 250 mg/kg IP, 3.5 h before sacrifice. Subchronically but not acutely administered salbutamol caused both a significant increase in endogenous noradrenaline (NA) levels and an increase NA utilization. Dopamine levels and turnover were, however, not altered by either acute or subchronic treatment. The activation, probably centrally elicited, of brain NA and 5-hydroxytryptamine systems by the subchronic salbutamol regimen supports the concept of beta-adrenoceptor mediated regulation of brain monoamine systems, and could contribute to the clinically reported antidepressant activity of beta-2-adrenoceptor agonists.