Acute effects of lithium on catecholamines, serotonin, and their major metabolites in discrete brain regions

Abstract

The acute effects of lithium on the central catecholamine and serotonin systems were investigated in well-defined cortical areas in the rat: the anterior cingulate cortex (CIN), the piriform-entorhinal region (PiEn), and the primary visual area (VIS) as well as in the hippocampus (HIP), the neostriatum (CPU; caudateputamen), and the olfactory bulbs (OBs). In these microdissected regions, the catecholamines noradrenaline (NA) and dopamine (DA), the indoleamine 5-hydroxytryptamine (5-HT; serotonin), as well as some of their major metabolites (3-methoxy-4-hydroxyphenylglycol; 3,4-dihydroxyphenylacetic acid; homovanillic acid; 3-methoxytyramine; 5-hydroxy-1-tryptophan; and 5-hydroxyindole-3-acetic acid) were assayed by using high-performance liquid chromatography (HPLC) with electrochemical detection. One hour after the administration of lithium chloride (2 and 10 mEq/kg; i.p.) the endogenous NA levels increased in the CIN and PiEn cortices, in the HIP, and in the CPU. The DA contents remained unchanged in the CPU, HIP, OB, and VIS cortex but were increased in the CIN and PiEn regions. These increases in cortical DA levels were accompanied by reductions in HVA and DOPAC. The levels of HVA and DOPAC but not 3-MT were also reduced in the CPU, in spite of a normal DA content. The discrepancies between changes of DA and the levels of its metabolites indicate changes in the turnover rates as well as an action of lithium on DA synthesis and/or storage in the nigrostriatal and mesocortical systems. The 5-HT contents were also increased by lithium throughout all regions, except for the OB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptive changes in the rat dopaminergic transmission following repeated lithium administration

“…There is no agreement in the literature concerning the effect of repeated administration of lithium on concentrations of DA and metabolites in the rat brain (e.g. Baptista et al, 1993;Berggren, 1985;Bliss and Ailion, 1970;Bowers and Rozitis, 1982;Carli et al, 1994;Corrodi et al, 1969;Friedman and Gershon, 1973;Gottberg et al, 1989;Ho et al, 1970;Mclntyre, 1983;Otero-Losada and Rubio, 1985;Poitou and Bohuon, 1975;Schubert, 1973).…”

The role of mood stabilisers in the treatment of the depressive facet of bipolar disorders

“…In fact, lithium is affective in controlling dopamine stimulants related behaviours (Acquas and Fibiger, 1996;Barnes et al, 1986;Carli et al, 1997b;Dziedzicka-Wasyleweska et al, 1996;Goodwin and Jamison, 1990;Gottberg et al, 1988Gottberg et al, , 1989Post and Weiss, 1995;Richelson, 1995).…”

Mood-Stabilizing Agents

“…Reported effects include alterations of the distribution of cations including Na , as well as subtle changes in neuronal membrane polarization. Lithium also interferes with the production, storage, and release of norepinephrine and dopamine and can increase their reuptake at cerebral nerve terminals, but may increase release of serotonin in forebrain [ 26,142,186,298,306 ] . In addition, lithium exerts complex effects on monoamine receptor functions, usually tending to reduce the functioning of adrenergic and other cerebral mechanisms implicated in mood elevation and behavioral activation, including preventing upregulation and supersensitivity of monoamine receptors in association with their long-term blockade, as well as exerting possible decreases in the sensitivity of excitatory glutamate receptors [ 89,98,261,269,284 ] .…”