Effects Of A Selective Cannabinoid Agonist And Antagonist On Body Temperature In Rats

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Carol A Paronis1, Ganesh A Thakur2, Kiran Vemuri2, Alex Makriyannis2 and Jack Bergman1

1 Preclinical Pharmacology/Mclean Hosp, Harvard Medical School, 115 Mill St, Belmont, MA, 02478,
2 Center for Drug Discovery, Northeasterm University, 360 Huntington Ave, 116 Mugar Life Sciences Hall, Boston, MA, 02115


The present study used changes in body temperature to characterize agonist and antagonist effects of cannabinoid (CB) receptor ligands in rats. The effects of two novel compounds, AM4054 and AM4113, were compared with {Delta}9THC and SR141716A. AM4054 is a cannabinoid structure with approximately 40-fold selectively for CB1 over CB2 receptors (CB1 Ki=2.2nmol). AM4113 is a pyrazole with approximately 400-fold selectively for CB1 over CB2 receptors (CB1 Ki=0.3nmol). Male rats (n=6/group) were loosely restrained while a rectal probe was inserted and taped to their tails; temperatures were recorded for 6hrs after drug injection. AM4054 (0.03—1.0 mg/kg) and {Delta}9THC (1.0—10.0 mg/kg) produced hypothermia whereas AM4113 and SR 141716A had no effects on body temperature. A dose of 1.0 mg/kg AM4054 decreased temperature by 5°C with a slow onset of effect; peak effects appeared 2—6 hrs after injection, depending on dose. {Delta}9THC also decreased temperature but had lesser effects than AM4054; 10.0 mg/kg {Delta}9THC decreased temperature by 2.4°C. The hypothermic effects of AM4054 were antagonized in a dose-dependent manner by SR141716A (0.3—1.0 mg/kg) and AM4113 (0.3—1.0 mg/kg). These data indicate AM4054 is a potent, slow onset, agonist at CB1 receptors and AM4113, in contrast, is a CB1 antagonist.

(Supported by NIH/NIDA: DA19205)

Source: Effects of a Selective Cannabinoid Agonist and Antagonist on Body Temperature in Rats