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How does the medication Lithium work on the brain in alleviating the symptoms of bipolar disorder?

Responses (3)

WildcatVet 25 Mar 2016

*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!

JakeMelboure 25 Mar 2016

Hi dagduncan.

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).

dagduncan 25 Mar 2016

Thank you Jake, that makes some sense. I just couldn't get the connection between salt and mood but I got some idea now...

JakeMelboure 26 Mar 2016

No worries.

Lithium pharmacology is definitely one of the more difficult ones I've learnt about.

Ultimately, a manic episode can be simplified to be explained as a global over-firing of the brains neurons (which use ions such as potassium, sodium and calcium to carry the electrical impulses along the neurons).

It's proposed that lithium may interfere with this abnormal firing... and hence terminate a manic episode.

Perhaps one day we'll understand exactly how it works.

Maybe...

Take care.
Jake.

masso 25 Mar 2016

Hi,

"Mechanism of action[edit]
The specific biochemical mechanism of lithium action in stabilizing mood is unknown.[1]

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.[50]

Unlike many other psychoactive drugs, Li+
typically produces no obvious psychotropic effects (such as euphoria) in normal individuals at therapeutic concentrations.[50] Lithium may also increase the release of serotonin by neurons in the brain.[51] 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.[52]

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