Sensitivity to delta9-tetrahydrocannabinol is selectively enhanced in beta-arrestin2 -/- mice.
Little is known about the roles of beta-arrestins in the regulation of brain CB1 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 CB1 receptors were investigated, including Delta-tetrahydrocannabinol, CP55940, methanandamide, JWH-073, and O-1812. Delta-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 CB1 agonists. Antagonist radioligand binding indicated no difference in the density of cannabinoid CB1 receptors in the cerebellum, cortex, or hippocampus of beta-arrestin2 +/+ and -/- mice. These data demonstrate that beta-arrestin2 may regulate cannabinoid CB1 receptor sensitivity in an agonist-specific manner.
Breivogel
Christopher S
CS
Department of Pharmaceutical Sciences, Campbell University School of Pharmacy Buies Creek, North Carolina 27506, USA. breivogel@campbell.edu
Lambert
Jonathan M
JM
Gerfin
Steven
S
Huffman
John W
JW
Razdan
Raj K
RK
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D019390:Arrestins / Q000235:genetics / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003511:Cyclohexanols / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011869:Radioligand Assay; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors; D000071557:beta-Arrestins
D001095:Arachidonic Acids; D019390:Arrestins; D003511:Cyclohexanols; C496820:O 1812; D043884:Receptor, Cannabinoid, CB1; D000071557:beta-Arrestins; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol