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The role of beta‐arrestin2 in the effects of chronic delta9‐tetrahydrocannbinol on cannabinoid receptors
Author(s) -
Puri Vanita,
Brievogel Christopher
Publication year - 2007
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.21.5.a410
Subject(s) - receptor , cannabinoid , cannabinoid receptor , beta (programming language) , endocrinology , medicine , chemistry , antagonist , pharmacology , biology , computer science , programming language
Beta‐arrestin2 appears to mediate downregulation of the G protein coupled receptors, but this has not been characterized for cannabinoid receptors. The role of beta‐arrestin2 in the regulation of brain CB 1 receptors was investigated in wild type and of beta‐arrestin2−/− mice. Chronic treatment of mice with 37.5 mg/kg delta 9 ‐tetrahydrocannbinol (THC) once/day for four days showed no difference in the development of tolerance; however, there were differences between wild type and beta‐arrestin2−/− mice in the number of antagonist‐precipitated withdrawal signs. Radioligand binding indicated that THC treatment decreased the number of CB 1 receptors in wild type mice, but did not affect the number of receptors in beta‐arrestin2−/− mice. These results indicated that the presence of beta‐arrestin2 does not appear to affect the development of tolerance, but does appear to affect the magnitude of dependence. Our studies also indicate that beta‐arrestin2 is required for down‐regulation of CB 1 receptors.