Cannabinoid action depends on phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons.

ABSTRACT: Herbal cannabis, smoked in the form of marihuana or hashish, is the most common illicit drug consumed in the Western world. In the brain, cannabinoids interact with neuronal CB1 receptors, thereby producing a marked reduction of motor activity. Here, we report that the motor depressant effect produced by the cannabinoid receptor agonist (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]trans-4-(3-hydroxypropyl)cyclohexanol (CP55,940) is attenuated by genetic inactivation of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), which is abundantly expressed in the medium spiny neurons of the striatum. Point mutation of Thr34, the protein kinase A (PKA) phosphorylation site of DARPP-32, produces a similar reduction in the effect of the CB1 agonist. In contrast, point mutation

SUBMITTER: Andersson M 

PROVIDER: S-EPMC6725667 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature