Here is an interesting article from ScienceNow.
Peace, John
2 March 1998 07:30 PM
How Lithium Quells a Manic Riot
Although lithium chloride has been the drug of choice for treating manic
depression for nearly a half-century, nobody has known how the drug acts to
quell the turbulent mood swings characteristic of the illness. Now a study
in tomorrow's issue of the Proceedings of the National Academy of Sciences
suggests that the drug protects nerve cells from being stimulated to death.
Because overstimulation is a hallmark of other brain diseases, such as
Huntington's and Parkinson's, the new results offer hope that lithium might
be useful in preventing the early stages of these maladies as well.
Lithium is often referred to as a mood-stabilizing drug for manic
depressives because it can prevent or reduce the number of manic
attacks--in which patients can become hyperactive and delusional--and
improve overall mood. Researchers have developed several theories, but
little proof, for what causes manic depression and how lithium helps
alleviate it. One theory holds that a manic-depressive person's brain
produces too much of the neurotransmitter glutamate, which binds to nerve
cell triggers called NMDA receptors. The relentless barrage of glutamate,
it's thought, might cause nerve cells to self-destruct in the hippocampus,
a brain region that helps control mood. Because some alternative
manic-depressive drugs work by blocking the NMDA receptor, De-Maw Chuang
and his colleagues at the National Institute of Mental Health in Bethesda,
Maryland, set out to test whether lithium counteracts the effects of excess
glutamate.
The researchers first added toxic amounts of glutamate to cultures of three
types of nerve cells: one found throughout the brain and the other two
specific to the cerebral cortex and hippocampus. In all three cultures,
half the neurons died within 24 hours, Chuang says. But when the
researchers added a dose of lithium roughly equivalent to the concentration
used in manic-depressive therapy, less than 10% of neurons died over the
same length of time. "To our surprise, this neuroprotective is very robust
and very long lasting," he says. As in manic-depressive patients treated
with lithium, the protection persisted for 24 hours after treatment was
stopped.
"It's a very interesting set of observations," says Steven Paul, vice
president of research at Eli Lilly and Co., which is testing new drugs for
treatment of manic depression. The study, he predicts, "will reinvigorate
efforts to understand how lithium really works." He notes that it's unclear
whether Chuang's results can be repeated in live animals. Such experiments
are already under way, Chuang says, with "encouraging results" so far. He's
looking forward to seeing lithium investigated for potential use in other
neural diseases in which NMDA receptors get too much stimulation. "This
raises the possibility that lithium could be used for protection in these
diseases as well," Chuang says.
