Sensitivity to delta9-tetrahydrocannabinol is selectively enhanced in beta-arrestin2 -/- mice.
Christopher S Breivogel, Jonathan M Lambert, Steven Gerfin, John W Huffman, Raj K Razdan
Behavioural Pharmacology July 2008 DOI: 10.1097/fbp.0b013e328308f1e6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study (knockout vs wild-type comparison) Peer reviewed |
|---|---|
| Population | Beta-arrestin2 knockout mice and wild-type littermates/counterparts |
| Interventions | Delta-tetrahydrocannabinol CP55940 methanandamide JWH-073 O-1812 |
| Measures | antinociception assay, body temperature measurement, antagonist radioligand binding |
| Topics | Cannabis |
| Key findings | Delta-tetrahydrocannabinol produced greater antinociception and greater decreases in body temperature in beta-arrestin2 knockout mice than in wild-type mice, while no significant differences were seen for CP55940, methanandamide, JWH-073, or O-1812. CB1 receptor density in cerebellum, cortex, and hippocampus did not differ between genotypes. The authors interpret these data as suggesting that beta-arrestin2 may regulate CB1 receptor sensitivity in an agonist-specific manner. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 6
- Serotonin, But Not N -Methyltryptamines, Activates the Serotonin 2A Receptor Via a β-Arrestin2/Src/Akt Signaling Complex In Vivo Journal of Neuroscience October 6, 2010
- 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 February 2015
- Mutation of putative GRK phosphorylation sites in the cannabinoid receptor 1 (CB1R) confers resistance to cannabinoid tolerance and hypersensitivity to cannabinoids in mice. Journal of Neuroscience April 9, 2014
- β-arrestin2 regulates cannabinoid CB1 receptor signaling and adaptation in a central nervous system region-dependent manner. Biological Psychiatry April 15, 2012
- Opposite function of dopamine D1 and N-methyl-D-aspartate receptors in striatal cannabinoid-mediated signaling. European Journal of Neuroscience November 2011
and 1 more in the library
Cites 3
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