Lithium: effects of short-term and chronic treatments in rats on the activity of dopamine-beta-hydroxylase (DBH) in the central versus peripheral nervous system

Abstract

The therapeutic usefulness of lithium in mania is now well-established. However, the precise neurochemical mechanisms by which lithium brings about its effects remain poorly understood. This report describes the effects of lithium on the central and peripheral levels of activity of dopamine-β-hydroxylase (DBH), the enzyme that catalyzes the final step in the biosynthetic pathway to the formation of norepinephrine (NE) from dopamine. Since the neurotransmitter NE has been implicated in the mediation of lithium's action, what effects lithium may have on the activity of DBH was deemed worth investigating. Lithium chloride was administered intraperitoneally in rats on a short-term and chronic basis and the effects on DBH activities in the hypothalamus and serum were evaluated. A significant reduction in DBH activity occurred in the hypothalamus after short-term lithium butthere was no change following chronic treatment. In contrast, serum DBH activity remained unchanged after both acute and chronic lithium injection. Since increased noradrenergic activity in the brain has been implicated in the etiology of mania, the lithium-induced decrease in hypothalamic DBH is suggestive of a neurochemical mechanism by which lithium may act in psychotic patients.