Baier looked at the genetic mutations in the "frozen" fish and found one in the glucocorticoid receptor, a protein that is found in almost every cell and that senses cortisol--a hormone involved in the stress response. In the normal response to a stressful situation, the hypothalamus in the brain sends corticotropin-releasing hormone (CRH) to the pituitary gland, which releases adrenocorticotropic hormone (ACTH) to the adrenal gland. The adrenal gland in turn produces cortisol. Cortisol then effectively reduces levels of ACTH and CRH, completing the normal response that allows both humans and zebrafish to deal with stress.
In the frozen fish, however, Baier found that levels of all three hormones--CRH, ACTH and cortisol--were higher than normal. He guessed that the animals were unable to respond properly to chronic stress--a problem that is known to trigger anxiety or depression in humans. On the basis of that diagnosis, he started putting the antidepressant fluoxetine (originally marketed as Prozac) in their water. After four days, they started swimming around normally. Other antidepressants and anxiolytics--drugs used to treat anxiety--also worked as a pick-me-up, he says. "There's a long literature on chronic stress being related to depression, but the causal link is unknown," says Baier. "Now we might be able to simulate this in fish and study it."
Other researchers suggest that Baier's findings may lead to the use of zebrafish to screen pharmaceuticals developed for humans.
Link | Photo: NIH