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Pro‐depressant‐like effects of CB1 receptor inverse agonists/antagonists in male Sprague‐Dawley rats
Author(s) -
Jutkiewicz Emily M,
Makriyannis Alexandros,
Vemuri Kiran,
Bergman Jack
Publication year - 2010
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.24.1_supplement.581.7
Subject(s) - depressant , rimonabant , inverse agonist , cannabinoid receptor , behavioural despair test , cannabinoid , pharmacology , tetrahydrocannabinol , agonist , amphetamine , psychology , receptor , medicine , psychiatry , antidepressant , dopamine , anxiety
Cannabinoid CB1 antagonists such as the inverse agonist rimonabant (SR141716A) or the neutral ligand AM 4113 may have therapeutic utility in the management of obesity and other disorders. However, adverse effects including depression may hinder their application, and preclinical means for predicting such effects have not been previously developed. In the present study, the effects of SR141716A and AM4113 were examined in a modified rat forced swim test that was optimized to measure increases in immobility (pro‐depressant‐like effects) in rats. In initial tests, reserpine and amphetamine withdrawal increased immobility, confirming clinical observations of pro‐depressant‐like effects. In subsequent testing, 10 mg/kg i.p. of SR141716A but not AM 4113, significantly increased immobility and decreased swimming in the forced swim test. To our knowledge, this is the first preclinical demonstration of pro‐depressant‐like effects with CB1 antagonists. These data also provide a preliminary suggestion that differences in pro‐depressant‐like effects of CB1 antagonism may be related to efficacy. Supported by USPHS grant DA19205.