(−)-Adamantyl-Δ8-tetrahydrocannabinol (AM-411), a selective cannabinoid CB1 receptor agonist: effects on open-field behaviors and antagonism by SR-141716 in rats

(−)-Adamantyl-Δ-tetrahydrocannabinol (AM-411) is a ‘classical’ tricyclic cannabinoid CB1 receptor agonist in which the C-3 alkyl side-chain has been replaced with an adamantyl group. The compound is cannabinoid CB1 receptor subtype selective (CB1Ki=6.86 nmol/l, CB2Ki=52.0 nmol/l). We examined the effects of AM-411 alone and in combination with the cannabinoid CB1 receptor antagonist/inverse agonist, SR-141716, on open-field behaviors of rats. The lowest effective dose of AM-411, 3 mg/kg, suppressed ambulation (horizontal activity) and rearing (vertical activity) and increased circling frequency compared to vehicle control levels. Co-administration of SR-141716 normalized these changes. SR-141716 (3 and 5.6 mg/kg) also produced significant increases in scratching and grooming (both frequency and duration), effects that were not eliminated in the presence of AM-411. Coupled with previous drug discrimination data, the open-field profile of AM-411 suggests that this high-affinity CB1 cannabinoid receptor agonist induces behavioral effects similar to the natural cannabinoid Δ-tetrahydrocannabinol and different from (R)-methanandamide, a chiral analog of the endogenous ligand anandamide.