Mice show how to calm anxiety

March 29, 2000 -- Scientists have found a genetic switch that helps calm anxiety in "stressed out" mice.

In three articles published in the April 2000 issue of the journal Nature Genetics, three independent groups of researchers report that Crhr2 (corticotropin-releasing hormone receptor-2), which is found in pituitary gland tissue and in other areas of the brain, actually quells the stress response in mice.

One of the leaders of the research efforts, Michael G. Rosenfeld, an HHMI investigator at the University of California, San Diego (UCSD), cautioned that the discoveries represent only a beginning in understanding the complexities of the stress response.

"It has long been known that many severe psychiatric disturbances show a heightening of the anxiety response," Rosenfeld said. "With these findings, we provide an initial motivation for further dissecting two distinct receptor systems in terms of potential drug discovery programs."

Rosenfeld's research group included his former UCSD colleague Toshimitsu Kishimoto, who is now at Yoshitomi Pharmaceuticals in Japan, and Jelena Radulovic and Joachim Spiess at the Max Planck Institute for Experimental Medicine in Germany. The other groups were from the Oregon Health Sciences University and The Salk Institute.

When a human or animal is stressed, the hypothalamus secretes the hormone, corticotropin-releasing hormone (Crh), which stimulates the pituitary gland to release additional hormones. These hormones from the pituitary gland cause the adrenal gland to secrete hormones that stoke the stress response, increasing anxiety, energy and blood pressure, and suppressing immune responses.

According to Rosenfeld, previous studies by his group and by other researchers revealed the existence of two distinct receptors for Crh -- Crhr1 and Crhr2 -- in the pituitary and in other brain regions involved

Contact: Jim Keeley
Howard Hughes Medical Institute

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