α2 adrenergic receptor trafficking as a therapeutic target in antidepressant drug action

Chapter

Abstract

  • Antidepressant drugs remain poorly understood, especially with respect to pharmacological mechanisms of action. This lack of knowledge results from the extreme complexity inherent to psychopharmacology, as well as to a corresponding lack of knowledge regarding depressive disorder pathophysiology. While the final analysis is likely to be multifactorial and heterogeneous, compelling evidence exists for upregulation of brain α adrenergic receptors (ARs) in depressed patients. This evidence has sparked a line of research into actions of a particular antidepressant drug class, the tricyclic antidepressants (TCAs), as direct ligands at α ARs. Our findings, as outlined herein, demonstrate that TCAs function as arrestin-biased ligands at α ARs. Importantly, TCA-induced α AR/arrestin recruitment leads to receptor endocytosis and downregulation of α AR expression with prolonged exposure. These findings represent a novel mechanism linking α AR trafficking with antidepressant pharmacology. 2 2A 2A 2A 2A 2
  • Authors

    Digital Object Identifier (doi)

    International Standard Book Number (isbn) 13

  • 9780128029398
  • Start Page

  • 207
  • End Page

  • 225
  • Volume

  • 132