Research explains lithium's dual anti-manic/ anti-depressive effect

John johnhkm at
Tue Sep 21 04:49:13 EST 1999

Old but I at least had always wondered why Cade's rats settled down.

Research explains lithium's dual anti-manic/ anti-depressive effect
As reported in the July 7 Proceedings of the National Academy of Sciences,
the researchers found that in mice brains, lithium exerts a push/pull effect
on the neurotransmitter glutamate, eventually causing it to level off in a
stable zone where it can control both extremes.

Under normal circumstances, an impulse from a nerve cell releases a flood of
message-bearing glutamate aimed at a neighboring neuron across the synapse.
A structure on the end of the releasing nerve cell, called a reuptake
transporter, then shuts off the signal by reabsorbing the glutamate, pumping
it back into the cell for reuse.

If the reuptake mechanism malfunctions, inappropriate concentrations of
neurotransmitter remain in the synapse. Hokin postulates abnormally low
glutamate levels are involved in depression, while elevated levels are
responsible for mania.

The research findings support clinical observations, he noted.

"It takes a few weeks before lithium begins to relieve depression and mania
in bipolar patients," he said. "It's now apparent an adaptive reuptake
mechanism that brings glutamate within a 'normal' range works over time to
curb both the highs and lows."


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