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To test this hypothesis, the researchers gave only progesterone to female rats lacking ovaries, then compared the acoustic startle response to female rats without ovaries injected with corn oil. The progesterone group displayed significantly lower CRF-enhanced startle responses. When ovariectomized females were tested with allopregnanolone alone it also reduced CRF-enahnced startle.

In a final experiment, the scientists compared the effects on females that received progesterone with those that received medroxy-progesterone, an artificial progestin that binds to progesterone receptors but does not metabolize into the progesterone metabolite allopregnanolone. Only natural progesterone reduced CRF-enhanced startle.

Previous studies have determined that allopregnanolone enhances the activity of GABA, the main inhibitory neurotransmitter in the central nervous system, at its receptors throughout the brain. This mechanism, Toufexis said, likely accounts for progesterone's blunting effect on the brain's stress system.

Findings from the study correlate with clinical evidence that some people suffering from depression or anxiety have low allopregnanolone levels that normalize after treatment with anti-depressant medications.

"New drugs could potentially be developed that mimic the effect of allopregnanolone on the GABA receptor, providing a new approach for controlling mood disorders in women," said Toufexis. "The next step is to determine where exactly allopregnanolone is working in the brain to reduce the effect of CRF."

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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University Health Sciences Center
8-Feb-2005