Premium
Physiological and behavioral effects of novel CB1‐receptor agonists AM 411 and AM 4054 in monkeys
Author(s) -
Delatte Marcus S,
Thakur G.,
Riolo Matthew,
Makriyannis Alexandros,
Bergman Jack
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a682-a
Subject(s) - antagonist , antagonism , agonist , cannabinoid , chemistry , cannabinoid receptor , cannabinoid receptor type 2 , inverse agonist , zoology , medicine , receptor , endocrinology , pharmacology , biology , biochemistry
Cannabinoid agonists such as D9‐THC can decrease operant responding and body temperature. These effects have been characterized in studies using the inverse agonist/antagonist SR 141716A to evaluate the CB1‐receptor mediated actions of cannabinoid agonists in rodents. The present studies in squirrel monkeys were conducted to further examine the effects of cannabinoid agonists on operant responding and colonic temperature by evaluating the effects of the novel ligands AM 411 and AM 4054 alone and after treatment with the neutral CB1‐receptor antagonist AM 4113. In behavioral studies, dose ranges for the rate‐decreasing effects of AM 411 (0.1–1 mg/kg) and AM 4054 (0.0032–0.032 mg/kg) first were established in monkeys (n=4) that responded under a fixed‐ratio 30 (FR30) schedule of milk delivery. The highest doses of both agonists decreased response rate to less than 20% of control values. The rate‐decreasing effects of 1 mg/kg AM 411 were blocked by the antagonist AM 4113 (1 mg/kg). In a separate group of monkeys (n=3), the effects of AM 411 and AM 4054 on colonic temperature were determined at an ambient temperature of 30°C. Doses of the agonists that maximally decreased operant responding also decreased colonic temperature by approximately 1°C. In antagonism studies, AM 4113 (0.32 mg/kg) attenuated the decreases in colonic temperature produced by AM 4054. Together, these results indicate that 1.) AM 4054 is more potent than AM 411 in decreasing response rate and colonic temperature; the effects of each agonist on these measures occur at comparable doses; the effects of AM 411 and AM 4054 appear to be mediated through CB1‐receptor mechanisms (Supported by PHS grant DA19205 and DA7252).