Salt Depletion Enhances Drug Response

Rats treated with diuretics to deplete their salt content became sensitized to amphetamine and developed an unusual pattern of neuronal growth in the part of the brain critical to motivation and reward. These findings were published in the May 23, 2002, online issue of the Journal of Neuroscience.

In the study, researchers from the University of Washington (UW, Seattle, USA) first gave diuretics to a group of rats to deplete them of salt. Then they gave the animals a 3% saltwater solution, a mixture they ordinarily would not like or drink. This procedure was repeated two more times, with each treatment given a week apart. Brain tissues from these rats were then examined under a microscope, and these showed that nerve cells in the nucleus accumbens (the area of the forebrain that controls behavior related to motivation and reward) had more branches and were 30-35% longer than normal.

In another set of experiments, salt-depleted rats were tested for cross sensitization to amphetamine. The rats were allowed to explore an open, dark plastic enclosure with the floor divided into a grid by white tape. The salt-depleted rats and a control group of animals were then injected with amphetamine and placed in the enclosure. The psychostimulant effects of the drugs were measured by two behaviors--the number of taped lines each animal crossed over and how many times it reared up on its hind feet. The two groups did not differ in the number of lines each crossed, but the salt-depleted rats showed significantly more rearing behavior.

It is not yet known whether these results can be related directly to humans. However, Dr. Ilene Bernstein, a UW psychologist who led the research, says, "The same part of the brain and the response to drugs holds up across species. The same systems are involved in rats and humans when it comes to amphetamines and cocaine. This suggests evidence of a common natural substrate to natural and artificial rewards that is worth further investigation.”

She added that the findings also point to questions that need to be explored. These include determining how long cross sensitization persists and whether physical challenges such as salt depletion alter people's responses to drugs.




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