Assessment of anandamide interaction with the cannabinoid brain receptor: SR 141716A antagonism studies in mice and autoradiographic analysis of receptor binding in rat

Anandamide is the newly discovered endogenous cannabinoid ligand that binds to brain cannabinoid receptors and shares most, but not all, of the pharmacological properties of D9-THC. Therefore, this study was undertaken to determine whether its interaction with the CB1 receptor in brain was identical to that of D9-THC. Anandamide depressed spontaneous activity and produced hypothermia, antinociception and immobility in mice after i.v. administration. However, none of these effects was blocked by pretreatment with the selective CB1 antagonist, SR 141716A. However, the metabolically stable analog 2-methyl-29-fluoroethylanandamide produced reductions in motor activ-ity and antinociception in mice, effects that were blocked by the antagonist. To determine whether anandamide’s receptor bind-ing mimicked that of other cannabinoids, an autoradiographi