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Alterations in 5-HT1B Receptor Function by p11 in Depression-Like States
Per Svenningsson,1,2Karima Chergui,2Ilan Rachleff,1Marc Flajolet,1Xiaoqun Zhang,2Malika El Yacoubi,3Jean-Marie Vaugeois,3George G. Nomikos,4Paul Greengard1*
The pathophysiology of depression remains enigmatic, althoughabnormalities in serotonin signaling have been implicated. Wehave found that the serotonin 1B receptor [5-hydroxytryptamine(5-HT1B) receptor] interacts with p11. p11 increases localizationof 5-HT1B receptors at the cell surface. p11 is increased inrodent brains by antidepressants or electroconvulsive therapy,but decreased in an animal model of depression and in braintissue from depressed patients. Overexpression of p11 increases5-HT1B receptor function in cells and recapitulates certainbehaviors seen after antidepressant treatment in mice. p11 knockoutmice exhibit a depression-like phenotype and have reduced responsivenessto 5-HT1B receptor agonists and reduced behavioral reactionsto 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.
* To whom correspondence should be addressed, E-mail: greengard{at}rockefeller.edu
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283, 19192-19200
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Evidence for a role of the 5-HT1B receptor and its adaptor protein, p11, in L-DOPA treatment of an animal model of Parkinsonism.
X. Zhang, P. E. Andren, P. Greengard, and P. Svenningsson (2008)
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281, 38905-38917
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Deletion of Annexin 2 Light Chain p11 in Nociceptors Causes Deficits in Somatosensory Coding and Pain Behavior.
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Serotonin transport and serotonin transporter-mediated antidepressant recognition are controlled by 5-HT2B receptor signaling in serotonergic neuronal cells.
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