Pharmacological enhancement of cannabinoid CB(1) receptor activity elicits an antidepressant-like response in the rat forced swim test
Hill MN, Gorzalka BB.
Department of Psychology,
University of British Columbia,
Vancouver, 2136 West Mall,
Canada V6T 1Z4.
Eur Neuropsychopharmacol. 2005 May 22


These experiments aimed to assess whether enhanced activity at the cannabinoid CB(1) receptor elicits antidepressant-like effects. To examine this we administered 1 and 5 mg/kg doses of the endocannabinoid uptake inhibitor AM404; 5 and 25 mug/kg doses of HU-210, a potent CB(1) receptor agonist; 1, 2.5 and 5 mg/kg of oleamide, which elicits cannabinoidergic actions; 1 and 5 mg/kg doses of AM 251, a selective CB(1) receptor antagonist, as well as 10 mg/kg desipramine (a positive antidepressant control) and measured the duration of immobility, during a 5-min test session of the rat Porsolt forced swim test. Results demonstrated that administration of desipramine reduced immobility duration by about 50% and that all of AM404, oleamide and HU-210 administration induced comparable decreases in immobility that were blocked by pretreatment with AM 251. Administration of the antagonist AM 251 alone had no effect on immobility at either dose. These data suggest that enhancement of CB(1) receptor signaling results in antidepressant effects in the forced swim test similar to that seen following conventional antidepressant administration.
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