Chronic treatment of human astrocytoma cells with lithium, carbamazepine or valproic acid decreases inositol uptake at high inositol concentrations but increases it at low inositol concentrations

Inositol uptake was measured at concentrations of 25, 40 and 50 mu M in hum an astrocytoma cell cultures treated for 1-3 weeks with pharmacologically r elevant concentrations of LiCl, valproic acid or carbamazepine as well as i n control cultures that had not been treated with any drug. After at least 2 weeks of treatment, each of these 3 conventional anti-bipolar drugs incre ased the uptake significantly at 25 mu M inositol, had no effect at 40 mu M and decreased it at 50 mu M inositol. Reduction of the drug concentrations by 50% abolished the stimulation of uptake at 25 mu M inositol by lithium and valproic acid and reduced that by carbamazepine. These findings may con tribute to an understanding of the mechanisms of action for anti-bipolar me dication, and explain the controversy in the literature whether or not brai n inositol is reduced after chronic administration of Lithium. (C) 2000 Pub lished by Elsevier Science B.V. All rights reserved.