The effects of beta-arrestin1 deletion on acute cannabinoid activity, brain cannabinoid receptors and tolerance to cannabinoids in mice

Journal of Receptor and Signal Transduction Research
C S Breivogel, Manan S Vaghela

Abstract

Previous studies have indicated a role for beta-arrestin2 in the regulation of brain cannabinoid effects and cannabinoid CB1 receptors, but whether beta-arrestin1 has a role has not been investigated. To determine the role of beta-arrestin1 in cannabinoid activity. Beta-arrestin1 -/- mice and their wild-type (+/+) counterparts were assayed for antinociceptive and temperature-decreasing effects of two ligands, Δ(9)-tetrahydrocannabinol (THC) and CP55940, after both single and repeated administration. In vitro assays examined the effects of deletion on CB1 receptor density, agonist-binding and G-protein activation. Deletion of beta-arrestin1 diminished the effects of CP55940 in both antinociception (latency to tail withdrawal) and temperature-depression assays in mice. However, deleting beta-arrestin1 had no effect on the actions of THC in either assay. Antagonist radioligand ([(3)H]SR141716A) saturation binding indicated no difference between beta-arrestin1 +/+ and -/- mice in the density or affinity for cannabinoid CB1 receptors in brain membranes. CP55940 agonist binding in brain membranes from beta-arrestin1 +/+ mice exhibited high- and intermediate-affinity sites, but beta-arrestin1 -/- membranes exhibited an additional site...Continue Reading

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Citations

Oct 19, 2016·Molecular Pharmacology·Carlos Nogueras-Ortiz, Guillermo A Yudowski
Apr 25, 2019·International Journal of Molecular Sciences·Rufaida Al-ZoubiPatricia H Reggio
Nov 14, 2018·The Journal of Pharmacology and Experimental Therapeutics·Catheryn D WilsonWilliam E Fantegrossi
Jul 1, 2020·Frontiers in Molecular Neuroscience·Alexandra Fletcher-JonesKevin A Wilkinson
Aug 11, 2020·Frontiers in Molecular Neuroscience·Andrew J Kesner, David M Lovinger
Jan 20, 2017·Frontiers in Cellular Neuroscience·Debra A Kendall, Guillermo A Yudowski

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