Comparison of the Effects of Losulazine and Reserpine on Central Aminergic Neurons

The purpose of this study was to examine the effects of both acute and chronic administration of the peripheral sympatholytic antihypertensive agent losulazine on central dopaminergic, noradrenergic, and 5-hydroxytryptaminergic neurons in the rat. For comparison, the acute effects of reserpine were also examined. Acute systemic administration of losulazine produced marked dose- and time-dependent decreases in dopamine and norepinephrine concentrations in regions outside the blood-brain barrier (i.e., the median eminence, intermediate lobe, and neural lobe), that were accompanied by an increase in plasma concentrations of prolactin and α-melanocyte-stimulating hormone. By comparison, losulazine caused a relatively modest, transient depletion of dopamine and norepinephrine (but not 5-hydroxytryptamine) in regions of the brain protected by the blood-brain barrier (i.e., the striatum, nucleus accumbens, and dorsomedial nucleus of the hypothalamus). In contrast to losulazine, acute systemic administration of reserpine caused a prolonged depletion of dopamine, norepinephrine, and 5-hydroxytryptamine in all brain and pituitary regions examined. These results suggest that regional differences in the response of aminergic neurons to acute administration of losulazine and reserpine reflect differences in the ability of these drugs to penetrate the blood-brain barrier. Chronic systemic administration of losulazine produced a similar decrease in dopamine and norepinephrine in the median eminence, intermediate lobe, and neural lobe, suggesting that tolerance does not develop to the ability of losulazine to deplete catecholamines in these regions. Chronic losulazine administration also decreased dopamine concentrations in the striatum, and norepinephrine concentrations in the dorsomedial nucleus, suggesting that losulazine may have cumulative effects on central catecholamine neurons terminating in these brain regions.