Sensitivity to Δ9-tetrahydrocannabinol is selectively enhanced in beta-arrestin2-/- mice

Little is known about the roles of beta-arrestins in the regulation of brain CBI cannabinoid receptors. This study investigated the role of beta-arrestin2 in cannabinoid behavioral effects using beta-arrestin2-/- mice and their wild-type counterparts. A variety of cannabinoid ligands from different chemical classes that exhibit a variety of efficacies for activation of CB(1) receptors were investigated, including Delta(9)-tetrahydrocannabinol, CP55940, methanandamide, JWH-073, and 0-1812. Delta(9)-tetrahydrocannabinol produced both greater antinociception and greater decreases in body temperature in beta-arrestin2 -/- compared with beta-arrestin2 +/+ mice. No significant differences were, however, present in either assay for the other CB, agonists. Antagonist radioligand binding indicated no difference in the density of cannabinoid CB, receptors in the cerebellum, cortex, or hippocampus of beta-arrestin2 +/+ and -/- mice. These data demonstrate that beta-arrestin2 may regulate cannabinoid CB, receptor sensitivity in an agonist-specific manner. Behavioural Pharmacology 19:298-307 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.