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Relevance of GPCR functional selectivity/biased signaling to drugs of abuse (468.1)
Author(s) -
Caron Marc,
Urs Nikhil,
Peterson Sean,
Daigle Tanya,
Snyder Joshua
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.468.1
Subject(s) - g protein coupled receptor , arrestin , signal transduction , neuroscience , g protein , dopamine , receptor , dopamine receptor d2 , functional selectivity , dopamine receptor , biology , microbiology and biotechnology , biochemistry
We now understand that GPCRs can signal not only through activation of G proteins but also through the ability of β‐arrestins to scaffold intracellular signaling molecules with distinct temporal and pharmacological properties. G protein‐ and β‐arrestin‐dependent signaling have been shown to mediate distinct cellular responses. We have previously demonstrated that both subfamilies of dopamine receptors, D1R and D2R, which are downstream targets of psychostimulant drugs of abuse, can signal through both G protein‐ and β‐arrestin‐mediated pathways. We have used genetic approaches to delete β‐arrestins globally or in selective neuronal populations to determine which signaling pathways mediate specific behavioral responses to various psychostimulants. Collectively, our data suggest that both G protein‐ and β‐arrestin‐dependent signaling play an important role in psychomotor responses whereas only G protein signaling downstream of dopamine receptors contributes predominantly to the reinforcing effects of psychostimulants. These findings suggest that developing functionally selective receptor‐based therapeutic approaches may represent a viable avenue to manage drugs of abuse.