Science 6 January 2006:
Vol. 311. no. 5757, pp. 77 - 80
Alterations in 5-HT1B Receptor Function by p11 in Depression-Like States
Per Svenningsson,1,2 Karima Chergui,2 Ilan Rachleff,1 Marc Flajolet,1 Xiaoqun Zhang,2 Malika El Yacoubi,3 Jean-Marie Vaugeois,3 George G. Nomikos,4 Paul Greengard1*
The pathophysiology of depression remains enigmatic, although abnormalities in serotonin signaling have been implicated. We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depression and in brain tissue from depressed patients. Overexpression of p11 increases 5-HT1B receptor function in cells and recapitulates certain behaviors seen after antidepressant treatment in mice. p11 knockout mice exhibit a depression-like phenotype and have reduced responsiveness to 5-HT1B receptor agonists and reduced behavioral reactions to an antidepressant.
1 Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA.
2 Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
3 Unite de Neuropsychopharmacologie Experimentale—CNRS FRE2735, European Institute for Peptide Research (IFRMP 23), Faculty of Medicine and Pharmacy, Rouen F76183 Cedex, France.
4 Neuroscience Discovery Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. |
