Discriminative stimulus effects of the cannabinoid CB1 receptor antagonist rimonabant in rats.

OBJECTIVE

To examine the discriminative stimulus effects of the cannabinoid CB(1) receptor (CB(1)R) antagonist/inverse agonist rimonabant (SR141716A) using a discriminated taste aversion (DTA) procedure.

MATERIALS AND METHODS

Groups of rats were trained to discriminate between drug (5.6 or 3 mg/kg) and vehicle in DTA (t' = 20 min). The 30-min drinking opportunity after rimonabant pretreatment was followed by injection of lithium chloride (120 mg/kg) in the experimental (EXP) animals. When offered fluid after vehicle pretreatment, EXP animals subsequently were given intraperitoneal saline (NaCl, 10 ml/kg). Post-drinking treatment for controls (CONT) was NaCl irrespective of the pretreatment condition (rimonabant or vehicle). Tests examined other doses and drugs (t' = 20 min).

RESULTS

The rimonabant analog AM251 (1 to 5.6 mg/kg) substituted for rimonabant. AM281 also appeared to substitute, but interpretation is complicated by unconditioned effects (drinking suppressed also in the CONT group). The CB(2)R antagonists SR144528 (18 and 30 mg/kg), AM630 (1 to 10 mg/kg), and the CB(1)R agonist methanandamide (mAEA, 3 and 10 mg/kg) did not substitute. There was a dose-related attenuation of the rimonabant-induced suppression of saccharin drinking when Delta9-tetrahydrocannabinol (Delta9-THC; 0.3 to 5.6 mg/kg), but not mAEA (1 to 10 mg/kg), was given together with rimonabant (3 mg/kg). Unconditioned effects occurred with the mAEA-rimonabant combination, not evident for combinations of rimonabant and Delta9-THC. mAEA (10 mg/kg) plus AM251 (5.6 mg/kg) resulted in strong unconditioned effects.

CONCLUSION

Rimonabant induces a discriminative stimulus in DTA that continues to show potential for further examination of cannabinoid receptor antagonism.