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Effects of lithium, alone or associated with pilocarpine, on muscarinic and dopaminergic receptors and on phosphoinositide metabolism in rat hippocampus and striatum.

Abstract：

:The mechanism of action of lithium (Li) alone or with pilocarpine (Pilo), focusing on muscarinic and dopaminergic systems and also on phosphoinositide metabolism was studied. Li (3 mEq/kg) administered to rats once (1 d) or daily for 7 days (7 d), 24 h before Pilo (15 mg/kg), exacerbated cholinergic signs, leading to tremors. convulsions and brain lesions. Increases in muscarinic receptors (MR) of 29 and 49% were observed in the hippocampus after atropine (Atro) and Li-Atro-Pilo treatments, respectively, as compared to controls (Atro) and the Li-Pilo group (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 D2-like receptors (D2R) was detected in the hippocampus in the group Li-7d. On the contrary, in the striatum an increase (25%) in the Li-7d group was observed and this effect was blocked by Li-Pilo. As far as inositol phosphates (IP) and phosphatidylinositol-4,5-biphosphate (PIP2) metabolism is concerned, Li caused a decrease (28%) and an increase (60%) in IP and PIP2 accumulations, respectively, in hippocampus slices while Pilo only altered IP accumulation (32% decrease). In this area the association of Li-Atro (10 mg/kg)-Pilo also caused a decrease (36%) in PIP2 as compared to the Li-Pilo group. In striatal slices, except for the Li, 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 detected. The potentiation of the effect of Pilo by Li does not seem to depend on the PI metabolism, but instead on its involvement with muscarinic and dopaminergic systems.

journal_name

Neurochem Int

journal_title

Neurochemistry international

authors

Marinho MM,de Sousa FC,de Bruin VM,Vale MR,Viana GS

doi

10.1016/s0197-0186(98)00028-x

subject

Has Abstract

pub_date

1998-10-01 00:00:00

pages

299-306

issue

eissn

0197-0186

issn

1872-9754

pii

S0197-0186(98)00028-X

journal_volume

pub_type

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Effects of lithium, alone or associated with pilocarpine, on muscarinic and dopaminergic receptors and on phosphoinositide metabolism in rat hippocampus and striatum.