In the current study, functioning slices of mice brain were examined following exposure to lithium, while control slices were not exposed to the drug. The researchers observed that lithium raised the glutamate level by slowing its reuptake. The higher the lithium dose, the greater the inhibition, they found.
To study the chronic effect of the lithium, the UW team administered it to live mice for two weeks. To their surprise, they saw that glutamate reuptake increased. This "up-regulation" resulted in less neurotransmitter in the synapse, which would produce an anti-manic effect.
"We were especially interested to find that the reuptake mechanism in the 18 lithium-treated mice was stabilized in a very narrow range, compared to the 18 controls," he said.
Hokin speculates a compensatory mechanism in the reuptake system strives over time to reset raised glutamate levels down into a fixed range. When the levels are too low, as postulated in depression, lithium brings them up into the stable region.
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."
What's more, he added, lithium doesn't change the moods of people who aren't bipolar, suggesting that their glutamate levels may be positioned consistently within the set zone, and therefore would not be affected by the drug.
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Contact: Lisa Brunette
brunette@macc.wisc.edu
608-263-5830
University of Wisconsin-Madison
7-Jul-1998