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Behavioral Characterization of Spiradoline and CP55,940 in Rats: Potential of Drug Mixtures for Treating Pain
Author(s) -
Minervini Vanessa,
France Charles Patrick
Publication year - 2016
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.30.1_supplement.703.3
Subject(s) - pharmacology , κ opioid receptor , opioid , agonist , cannabinoid , chemistry , nociception , receptor , medicine , anesthesia
Pain is a significant clinical problem and there is a need for drugs that are more effective with less adverse effects. Previous studies have shown that cannabinoid receptor agonists enhance the antinociceptive effects of mu opioid receptor agonists. It is unknown whether the well‐documented antinociceptive effects of kappa opioid receptor agonists are enhanced by cannabinoids and, therefore, whether kappa opioid receptor agonists, which are devoid of abuse liability, might be clinically useful in a drug mixture for treating pain. Cumulative dose‐effect functions (30‐min inter‐injection interval) were determined for the kappa opioid receptor agonist spiradoline (0.032 – 32.0 mg/kg) and the cannabinoid receptor agonist CP55,940 (0.0032 – 1.0 mg/kg) in 8 male Sprague Dawley rats for antinociception, schedule‐controlled behavior, body temperature, and diuresis. Spiradoline and CP55,940 dose dependently increased the latency for rats to remove their tails from warm (50°C) water to 100% of the maximum possible effect (20 s), while eliminating responding for food and decreasing body temperature by 5°C. CP55,940 was approximately 20‐ and 6‐fold more potent than spiradoline in the antinociception and the schedule‐controlled responding procedures, respectively. Spiradoline was 18‐fold and CP55,940 was 5‐fold more potent in the schedule‐controlled responding procedure than in the antinociception procedure. For both drugs, the rank order potencies across assays were schedule‐controlled responding > body temperature > antinociception. Spiradoline significantly increased (7‐fold) diuresis at doses that eliminated schedule‐controlled responding, whereas CP55,940 did not have a significant effect on urine output. These results provide the basis for examining mixtures of spiradoline and CP55,940 to test whether the preferred and potentially clinically useful effects of kappa opioid receptor agonists (antinociception) are selectively enhanced by cannabinoid receptor agonists. Support or Funding Information This work was supported, in part, by NIDA grants K05DA017918 and T32DA031115.