*Based on findings from animal models, we hypothesize that lithium downregulates the presynaptic 5-HT1A receptor, upregulates the postsynaptic 5-HT1A receptor, and upregulates 5-HTT. We obtained pilot funding to perform PET scanning of the 5-HT1A and 5-HTT systems in bipolar depressed subjects before and after a therapeutic course of lithium monotherapy.*
*Lithium affects the flow of sodium through nerve and muscle cells in the body. Sodium affects excitation, depression, and mania.*
Now we just need a biochemist to explain that to us!
That's an interesting question which unfortunately, is widely debated and somewhat not fully understood.
As mentioned above, lithium is believed to down-regulate 5-HT1A (Serotonin 1A) receptors, which are inhibitory autoreceptors. In that way, it stimulates the release of serotonin (through disinhibition), which may contribute to its antidepressive properties. It's also believed to stimulate the production and release of serotonin from pre-synaptic neurons.
It also changes the normal resting ion exchange between the neurons in the brain, which is believed to be involved in its antimanic properties.
Other studies have found that it's effects on the phosphatidylinositol signalling pathways may underlie it's mood stabilising effects. (Though I don't understand this connection at all).
Sadly, like many of the psychotropic medications... I've come to accept that we don't really know exactly how or why it works. Just that clinically... it works quite well. We pretty much discovered lithium salts' mood stabilising effects by accident anyway.
Even I have to admit with all the study and training I've done, there is still a lot more about psychotropic medications (all medications, actually) that I don't know, than what I do.
Sorry we don't have the answers, but hopefully that helps. Perhaps someone with a more pure background in pharmacology than a clinical background can offer more evidence or insight as to how it works.
"Mechanism of action
The specific biochemical mechanism of lithium action in stabilizing mood is unknown.
Upon ingestion, lithium becomes widely distributed in the central nervous system and interacts with a number of neurotransmitters and receptors, decreasing norepinephrine release and increasing serotonin synthesis.
Unlike many other psychoactive drugs, Li+
typically produces no obvious psychotropic effects (such as euphoria) in normal individuals at therapeutic concentrations. Lithium may also increase the release of serotonin by neurons in the brain. In vitro studies performed on serotonergic neurons from rat raphe nuclei have shown that when these neurons are treated with lithium, serotonin release is enhanced during a depolarization compared to no lithium treatment and the same depolarization.
Several authors proposed that pAp-phosphatase could be one of the therapeutic targets of lithium. This hypothesis was supported by the low Ki of lithium for human pAp-phosphatase compatible within the range of therapeutic concentrations of lithium in the plasma of people (0.8–1 mM). Importantly, the Ki of human pAp-phosphatase is ten times lower than that of GSK3β (glycogen synthase kinase 3β). Inhibition of pAp-phosphatase by lithium leads to increased levels of pAp (3′-5′ phosphoadenosine phosphate), which was shown to inhibit PARP-1
Another mechanism proposed in 2007 is that lithium may interact with nitric oxide (NO) signalling pathway in the central nervous system, which plays a crucial role in the neural plasticity. The NO system could be involved in the antidepressant effect of lithium in the Porsolt forced swimming test in mice. It was also reported that NMDA receptor blockage augments antidepressant-like effects of lithium in the mouse forced swimming test, indicating the possible involvement of NMDA receptor/NO signaling in the action of lithium in this animal model of learned helplessness.
Lithium possesses neuroprotective properties by preventing apoptosis and increasing cell longevity."
- Lithium Information for Consumers
- Lithium Information for Healthcare Professionals (includes dosage details)
- Side Effects of Lithium (detailed)
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