EFFECTS OF LITHIUM, ALONE OR ASSOCIATED WITH PILOCARPINE, ON MUSCARINIC AND DOPAMINERGIC RECEPTORS AND ON PHOSPHOINOSITIDE METABOLISM IN RAT HIPPOCAMPUS AND STRIATUM

The mechanism of action of lithium (Lj) alone or with pilocarpine (Pil o), focusing on muscarinic and dopaminergic systems and also on phosph oinositide metabolism was studied. Li (3 mEq/kg) administered to rats once (1 d) or daily for 7 days (7 d), 24 h before Pile (15 mg/kg, exac erbated cholinergic signs, leading to tremors. convulsions and brain l esions. Increases in muscarinic receptors (MR) of 29 and 49% were obse rved in the hippocampus after atropine (Atro) and Li-Atro-Pilo treatme nts, respectively, as compared to controls (Atlo) and the Li-Pilo grou p (Li-Atro-Pilo). In the striatum, except for the 37% increase in the Li-Atro (50 mg/kg)-Pilo group as compared to the Li-Pilo one, no other changes were observed in MR. A decrease of 32% on average in D-2-like receptors (D2R) was detected in the hippocampus in the group Li-7d. O n the contrary, in the striatum an increase (25%) in the Li-7d group w as observed and this effect was blocked by Li-Pilo. As far as inositol phosphates (IP) and phosphatidylinositol-4,5-biphosphate (PIP2) metab olism is concerned, Li caused a decrease (28%) and an increase (60%) i n IP and PIP2 accumulations, respectively, in hippocampus slices while Pile only altered IP accumulation (32% decrease). In this area the as sociation of Li-Atro (10 mg/kg)-Pilo also caused a decrease (36%) in P IP2 as compared to the Li-Pilo group. In striatal slices, except for t he Lit Atro (10 mg/kg) and Li-Atro (10 mg/kg)-Pilo groups which showed a decrease (33-40%) in IP accumulation, no other alteration was detec ted. The potentiation of the effect of Pile by Li does not seem to dep end on the PI metabolism, but instead on its involvement with muscarin ic and dopaminergic systems. (C) 1998 Elsevier Science Ltd. All rights reserved.