Short- and Long-Term Lithium Administration: Effects on the Brain's Serotonergic Biosynthetic Systems

Abstract

Short-term treatment with lithium chloride stimulates the uptake of tryptophan and its conversion to serotonin by striate synaptosomes. Preincubation of striate synaptosomes with L-tryptophan and in vivo administration of L-tryptophan appear to act in a similar manner. Midbrain tryptophan hydroxylase activity is reduced in temporal continuity with the lithium-induced activation of tryptophan uptake and conversion. By 10 days, conversion of tryptophan to serotonin in nerve endings becomes a joint function of the maintained increased uptake of tryptophan and a decreased level of tryptophan hydroxylase activity in nerve endings. The occurrence of this delayed alteration corresponds in time to the previously described axoplasmic flow rate for tryptophan hydroxylase.

Effect of Serotonin Depletion Induced by <i>p</i>-Chloroamphetamine on Changes in Rats’ Activity Levels Produced by Lithium

“…As for NE transmis sion, it has been suggested that the increase in NE turnover observed after short-term lith ium administration is followed several weeks later by a relatively steady state [8]. The observed increase in 5-HT brain levels after 21-day lithium administration is in agree ment with previous reports showing in creases in 5-HT synthesis by as much as 80% [6,20], It has been suggested [11,12,15,22] that short-term administration of lithium in creases 5-HT synthesis by increasing precur sor uptake, and that continued lithium ad ministration, after 10-21 days, leads to a compensatory decrease in tryptophan hy droxylase activity which eventually brings 5-HT synthesis back to a normal, although 'buffered', state. Since our brain assays were performed on the 21st day, it is difficult to say if the small, although significant, 20% increases in 5-HT levels represent a phase in the gradual return from increased to normal levels, or if it reflects the attainment of steady higher baseline levels.…”

Long-Term Lithium Treatment Causes Serotonin Receptor Down-Regulation via Serotonergic Presynapses in Rat Brain

“…Regarding possible participation o f presynaptic mechanisms in the lithium action, short-term treatment with lithium was reported to potentiate the tryptophan uptake and the 5-HT synthesis [Knapp and Mandell, 1973], and to cause 5-HT superactivity syndromes in rats [Grahame-Smith and Green, 1974], It has been suggested recently that the head twitches (head shakes or 'wet dog shakes') induced by the admin istration o f 5-HT precursors or 5-HT agonists in the rats are mediated by 5-HT2 receptors [Peroutka et al, 1981;Lucki et al, 1984], On the basis o f these and other reported findings, the present study was carried out to obtain further informa tion about the mechanism o f the lithium action. The effects o f lithium treatment o f rats on 5-HT receptor bindings, 5-hydroxytryptophan (5-HTP)-induced head twitches and the 5-HT turnover were investigated in rats.…”

The Effect of Lithium on the Increase in Forebrain 5‐hydroxyindoleacetic Acid Produced by Raphe Stimulation

“…The effect of chlorimipramine was analysed by the Student's t test: *P < 0.05; **P < 0.001. Table 4 The effect of chlorimipramine in vitro (4 x 10-7 M) on the synaptosomal uptake of 5-hydroxytryptamine (5-HT) in the presence or absence of Li' in the incubation medium 5-HT uptake (pmol/mg protein) Control Lithium preted as being due to an increase in the synthesis and turnover of 5-HT (Knapp & Mandell, 1973;Poitou, Guerinot & Bohoun, 1974). Treatment with Li' for 10 days or more appears to have little effect on turnover (Bliss & Ailion, 1970;Knapp & Mandell, 1973), and it has been suggested that the increase in 5-HIAA following 10 day Li+ treatment may result in part from an impairment of the storage mechanism within 5-HT terminals (Collard & Roberts, 1977).…”