(-)-Adamantyl-delta8-tetrahydrocannabinol (AM-411), a selective cannabinoid CB1 receptor agonist: effects on open-field behaviors and antagonism by SR-141716 in rats.
(-)-Adamantyl-Delta8-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 (CB1 Ki=6.86 nmol/l, CB2 Ki=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 Delta9-tetrahydrocannabinol and different from (R)-methanandamide, a chiral analog of the endogenous ligand anandamide.
Järbe
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TU
Temple University, Department of Psychology, Philadelphia, Pennsylvania 19122, USA. tjarbe@astro.temple.edu
DiPatrizio
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NV
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D
Makriyannis
A
A
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids / Q000037:antagonists & inhibitors; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant
C496392:(-)-adamantyl-delta8-tetrahydrocannabinol; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D013759:Dronabinol; D000218:Adamantane; D000077285:Rimonabant