Depressed Fish Provide Evidence of Possible Link Between Antidepressants and Stress Hormones

September 23, 2013- Mutated zebrafish have become a new ally in the search for new drug treatments for depression.

ScienceDaily is reporting on new research that shows fluoxetine, the antidepressant commonly know under the trade name Prozac, normalizes the behavior of zebrafish exhibiting a genetic mutation for a defective stress hormone receptor.

Scientists at the Max Planck Institute of Neurobiology in Martinsried, Germany, working with Director Herwig Baier, found that, as with humans, chronic stress for fish can lead to anxiety and depression.

Under normal circumstances, the hormone cortisol helps both fish and humans regulate stress. The team managed to identify zebrafish with a genetic mutation that lack the receptor for cortisol, resulting in a consistently high level of stress when faced with an unfamiliar new environment.

When an antidepressant was added to the water, the behavior of these returned to normal, thus demonstrating a direct causal link between chronic stress and depression.

The findings indicate many possible search strategies for new drugs to treat psychiatric disorders.

Under stress, the body releases hormones in preparation for "fight or flight", or perhaps in this case, "fight or swim." Hormone levels return to normal eventually, but if they do not, chronic stress may occur which can lead to depression and anxiety. It remains unclear whether stress is a trigger or just a side effect.

The evidence of cause and effect between stress and depression was unexpected. The researchers found zebrafish suffering from stress resulting from a genetic mutation also showed signs of behavioral depression. When introduced into a new tank, affected fish sank to the bottom of the tank, remaining inert for a long time before becoming used to the new environment.

Results showed that a mutation in the glucocorticoid receptor prevented cortisol from binding (and thereby restricting the release of stress hormones). Unable to regulate the production release of stress hormones, the levels remain high.

To test the hypothesis that the mutated fish were suffering from chronic stress and exhibiting depression, the researchers added fluoxetine to the water. Sure enough, their behavior was very shortly normalized.

Herwig Baier said, "Although there are a whole range of drugs available for depression, no one yet knows what the relationship is between their effect and the stress hormones. Our findings provide the first evidence of a possible connection."

Read the full post here.

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