Chronic stress and antidepressant treatment have opposite effects on P-glycoprotein at the blood-brain barrier: an experimental PET study in rats

Journal of Psychopharmacology
Onno L de KlerkPeter Meerlo

Abstract

The multi-drug efflux transporter P-glycoprotein is expressed in high concentrations at the blood-brain barrier and has a major function in the transport of drugs. In a recent PET-study evidence was found for an increased function of P-glycoprotein at the blood-brain barrier in medicated patients suffering from major depressive disorder. We used small-animal PET and [(11)C]-verapamil to study P-glycoprotein function at the blood-brain barrier of rats, either being administered as venlafaxine, an antidepressant, or subjected to chronic stress, a factor contributing to the development of depression. In a first experiment, male Wistar rats underwent a three-week foot shock procedure as a model of human depression. In a second experiment, rats were chronically treated with the antidepressant venlafaxine (25 mg/kg/d via an implanted osmotic minipump). In both experiments, a [(11)C]-verapamil PET scan was performed. In the chronically stressed rats, the distribution volume (V(T)) of [(11)C]-verapamil was significantly increased, whereas treatment with venlafaxine had the opposite effect and caused a significant reduction in V(T). The changes in V(T) could not be attributed to the influx rate constant (K(1)). Our data suggest that P-g...Continue Reading

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Citations

Nov 5, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xueqian WangDavid S Miller
Sep 30, 2010·The International Journal of Neuropsychopharmacology·Yan LinEric A Stone
Jan 23, 2015·Frontiers in Behavioral Neuroscience·Georgia BalsevichMathias V Schmidt
Nov 25, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Christoffer BundgaardMats Garmer
Oct 13, 2021·Cellular and Molecular Neurobiology·Shusheng WuLongfei Du

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