Levels, Metabolism, and Pharmacological Activity of Anandamide in CB1 Cannabinoid Receptor Knockout Mice

摘要: Anandamide [arachidonylethanolamide (AEA)] appears to be an endogenous agonist of brain cannabinoid receptors (CB(1)), yet some the neurobehavioral effects this compound in mice are unaffected by a selective CB(1) antagonist. We studied levels, pharmacological actions, and degradation AEA transgenic lacking gene. quantified other endocannabinoid, 2-arachidonoyl glycerol, six regions spinal cord isotope-dilution liquid chromatography-mass spectrometry. The distribution endocannabinoids their inactivating enzyme, fatty acid amide hydrolase, were found overlap with only part. In knockout homozygotes (CB(1)-/-), hippocampus and, lesser extent, striatum exhibited lower levels as compared wild-type (CB(1)+/+) controls. These data suggest ligand/receptor relationship between these two regions, where tonic activation receptor may tightly regulate biosynthesis its ligand. 2-Arachidonoyl glycerol hydrolase activity unchanged CB(1)-/- respect CB(1)+/+ all regions. Delta(9)-tetrahydrocannabinol (THC) tested for capability inducing analgesia catalepsy decreasing spontaneous activity. AEA, unlike THC, not decreased mice. but stimulated GTPgammaS binding membranes from mice, stimulation was insensitive CB(2) antagonists. that non-CB(1), non-CB(2) G protein-coupled might mediate neuro-behavioral actions AEA.