Discriminative stimulus effects in rats of SR-141716 (rimonabant), a cannabinoid CB1 receptor antagonist

Objective To examine the discriminative stimulus effects of (i) the cannabinoid CB₁ receptor antagonist SR-141716 (SR, 5.6 mg/kg) and vehicle, and (ii) the cannabinoid receptor agonist ⁹-THC (THC, 1.8 mg/kg) and vehicle using a discriminated taste aversion (DTA) procedure.Methods Two groups of rats (n=6) were trained to discriminate between these drugs and vehicle in DTA (t=20 min). The 30-min drinking bout of tap water following drug (SR or THC) treatment was followed by an injection of lithium chloride (LiCl, 120 mg/kg) in the experimental animals. When offered water after vehicle pretreatment, experimental animals subsequently were given IP saline (NaCl, 10 ml/kg). Post-drinking treatment for controls (n=6) was NaCl, irrespective of the pretreatment condition (SR, THC or vehicle). Additional water was provided during the afternoon (30 min) with no other manipulations. Food was available ad lib at all times. When the discriminations were established other doses and drugs were examined (t=20 min). In testing there were no post-drinking treatments.Results The SR-related analog AM-251 (dose range: 1–5.6 mg/kg) substituted for SR, whereas other drugs such as the cannabinoid CB₂ receptor antagonist SR-144528 (3 and 10 mg/kg), THC (1–10 mg/kg), flumazenil (1–10 mg/kg), naloxone (1–10 mg/kg), morphine (10 and 18 mg/kg) and d-amphetamine (1 and 3 mg/kg) did not. There was a dose-related attenuation of SR-induced suppression of drinking when THC (1.8–10 mg/kg) was given together with SR (5.6 mg/kg). In the THC trained rats, SR (1–10 mg/kg), morphine (10 and 18 mg/kg) and d-amphetamine (1 and 3 mg/kg) did not substitute for THC. SR (1 mg/kg) attenuated the THC (1.8 mg/kg) induced suppression of drinking. Together with 3 mg/kg SR and 1.8 mg/kg THC, drinking was roughly equally suppressed in both the experimental group and the controls.Conclusion SR-141716 induces a discriminative stimulus complex in DTA that shows potential for further examination of cannabinoid receptor antagonism.