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Re: Is the LITHIUM causing this? SLS

Posted by Sunnely on October 1, 2001, at 19:14:18

In reply to Re: Is the LITHIUM causing this?, posted by SLS on October 1, 2001, at 8:11:46

> Hi Sunnely.
>
> By what mechanisms does lithium exert its pro-serotonergic effects?
>
> Thanks.
>
>
> - Scott

Hi Scott,

Exactly, I don't know. It appears that lithium enhances tryptophan uptake and has various other indirect effects on serotonin metabolism.

Here's an excerpt from a book explaining lithium's pro-serotonergic effect.

Many studies have shown that lithium affects the synthesis, turnover, release, and uptake of the monoamine neurotransmitter 5-hydroxytryptamine (serotonin; 5-HT). Furthermore, it enhances the effects of serotonergic antidepressant drugs, particularly in cases of tricyclic-resistant depression. Although the number (Bmax) and function of 5-HT2A receptors are modulated by several antidepressant therapies, lithium's effects on this serotonin receptor subtype is not straightforward. The 5-HT2 family of serotonin receptors is of particular interest because it activates, through a guanine nucleotide binding protein (G protein) linkage, the hydrolysis of phospholipase C (PLC), which activates the diacyglycerol (DAG) and inositol 1,4,5-triphosphate (IP3) second-messenger systems. Lithium's involvement in modulating 5-HT2A receptor function is probably not a simple matter of it altering receptor number or affinity, because many investigations have failed to show a consistent effect. The functional consequences of lithium on 5-HT2A receptor activity, as measured by behavioral responses, are equally ambiguous.

Reference: Bipolar Medications: Mechanisms of Action, 2000. Edited by Husseini K. Manji, MD, Charles L. Bowden, MD, and Robert H. Belmaker, MD. American Psychiatric Press, Inc., Washington, DC.


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