EFFECTS OF LITHIUM TREATMENT INVITRO AND INVIVO ON ACETYLCHOLINE METABOLISM IN RAT-BRAIN

Abstract— The effects of LiCl on cholinergic function in rat brain in vitro and in vivo have been investigated. The high affinity transport of choline and the synthesis of acetylcholine in synaptosomes were reduced when part (25‐75%) of the NaCl in the buffer was replaced with LiCl or sucrose. This appeared to be due to lack of Na+ rather than to Li+, as addition of LiCl to normal buffer had little effect. Following an injection of LiCl (10mmol/kg, i.p.) into rats the concentration of a pulsed dose of [2H4]choline (20 μmol/kg, i.v., 1 min) and its conversion to [2H4]acetylcholine, and the concentrations of [2H2]acetylcholine and [2H0]choline were measured in the striatum, cortex, hippocampus and cerebellum. The [2H4]choline and [2H4]acetylcholine were initially (15 min after LiCl) reduced (to −30% in the cortex) and later (24 h after LiCl) increased (to + 50% in the striatum). There was a corresponding initial increase (to +50% in the cerebellum) and later decrease (to −30% in the hippocampus) of the endogenous acetylcholine and choline. These results indicate an initial decrease and later increase in the utilization of acetylcholine after acute treatment with LiCl. Following 10 days of treatment with LiCl there was an increased rate of synthesis of [2H4]acetylcholine from pulsed [2H4]choline in the striatum, hippocampus and cortex (P < 0.05). The high affinity transport of [2H4]choline and its conversion to [2H4]acetylcholine was activated (131% of control; P < 0.01) in synaptosomes isolated from brains of 10‐day treated rats. Investigation of synaptosomes isolated from striatum, hippocampus and cortex revealed that only striatal [2H4]acetylcholine synthesis was significantly stimulated. Kinetic analysis demonstrated that the apparent KT for choline was decreased by 30% in striatal synaptosomes isolated from rats treated for 10 days with LiCl. Striatal synaptosomes from 10‐day treated rats compared to striatal synaptosomes from untreated rats also released acetylcholine at a stimulated rate in a medium containing 35 mM‐KCl. These results indicate that LiCl treatment stimulates cholinergic activity in certain brain regions and this may play a significant role in the therapeutic effect of LiCl in neuropsychiatric disorders. Copyright © 1979, Wiley Blackwell. All rights reserved