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Effects of a CB1 receptor antagonist and 5‐HT2C receptor agonist alone and in combination on motivation for palatable food: a dose‐addition analysis study in mice
Author(s) -
Ward Sara Jane,
Lefever Timothy W,
Jackson Cavario,
Tallarida Ronald J,
Walker Ellen A
Publication year - 2007
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.21.6.a781
Subject(s) - agonist , cannabinoid , cannabinoid receptor , pharmacology , serotonin , chemistry , antagonist , rimonabant , potency , receptor antagonist , cannabinoid receptor agonists , receptor , partial agonist , endocrinology , cannabinoid receptor type 2 , medicine , cannabinoid receptor antagonist , 5 ht receptor , anorectic , food intake , biochemistry , in vitro
The cannabinoid and serotonin systems modulate feeding behavior in humans and laboratory animals. The present study assessed whether a cannabinoid CB1 receptor antagonist and a serotonin 5‐HT2C receptor agonist alone and in combination attenuate motivation for a food reinforcer as measured by a progressive ratio (PR) schedule of reinforcement in mice. Pretreatment with either the CB1 receptor antagonist SR141716A (SR; 0.3– 30.0 mg/kg) or the 5‐HT2C receptor agonist m‐chlorophenylpiperazine (mCPP; 0.1 – 10.0 mg/kg) dose‐dependently attenuated responding for the liquid nutritional drink Ensure® in male C57BL/6 mice. The relative potency of each drug alone was quantified and ED25s for SR and mCPP were determined to be 2.3 mg/kg and 0.30 mg/kg respectively. Fixed proportions of SR/mCPP mixtures in a 1:1 ratio based on their relative potencies were then administered and also dose‐dependently attenuated responding for liquid Ensure®. Dose‐addition analysis comparing the experimentally determined potency for SR/mCPP with the predicted additive potency revealed that SR/mCPP produced a significant synergistic attenuation of responding for Ensure®. These results support other findings that both the cannabinoid CB1 and serotonin 5‐HT2C receptor systems are involved in feeding behavior and suggest that these receptor systems can synergistically modulate motivation for palatable food.