Valium Research Today is a free monthly online journal that collates and summarizes the latest research about Valium, including details on diazepam, depression, side-effects, withdrawal.

Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions.

Fernández AP, Serrano J, Tessarollo L, Cuttitta F, Martínez A

Department of Cellular, Molecular, and Developmental Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain.

The adrenomedullin (AM) gene, adm, is widely expressed in the central nervous system (CNS) and several functions have been suggested for brain AM. Until now, a formal confirmation of these actions using genetic models has been elusive since the systemic adm knockout results in embryo lethality. We have built a conditional knockout mouse model using the Cre/loxP approach. When crossed with transgenic mice expressing the Cre recombinase under the tubulin Talpha-1 promoter, we obtained animals with no AM expression in the CNS but normal levels in other organs. These animals lead normal lives and do not present any gross morphological defect. Specific areas of the brain of animals lacking CNS AM contain hyperpolymerized tubulin, a consequence of AM downregulation. Behavioral analysis shows that mice with no AM in their brain have impaired motor coordination and are hyperactive and overanxious when compared to their wild-type littermates. Treatment with methylphenidate, haloperidol, and diazepam did not show differences between genotypes. Circulating levels of adrenocorticotropic hormone and corticosterone were similar in knockout and wild-type mice. Animals with no brain AM were less resistant to hypobaric hypoxia than wild-type mice, demonstrating the neuroprotective function of AM in the CNS. In conclusion, AM exerts a beneficial action in the brain by maintaining homeostasis both under normal and stress conditions.

Published 27 August 2008 in Proc Natl Acad Sci U S A, 105(34): 12581-6.
Full-text of this article is available online (may require subscription).

© 2004-2008 Valium Research Today. All Rights Reserved.