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

• Published in: Psychopharmacology 2008-07, Vol.198 (4), p.467-478
• Main Authors: Järbe, Torbjörn U. C., Li, Chen, Vadivel, Subramanian K., Makriyannis, Alexandros
• Format: Article
• Language: English
• Subjects: Animals; Antagonist drugs; Arachidonic Acids - pharmacology; Avoidance Learning - drug effects; Biomedical and Life Sciences; Biomedicine; Bornanes - pharmacology; Discrimination (Psychology) - drug effects; Discrimination Learning - drug effects; Dose-Response Relationship, Drug; Drinking - drug effects; Dronabinol - pharmacology; Drug dosages; Hallucinogens - pharmacology; Indoles - pharmacology; Injections, Intraperitoneal; Lithium Chloride - pharmacology; Male; Neurosciences; Original Investigation; Pharmacology; Pharmacology/Toxicology; Piperidines - administration & dosage; Piperidines - pharmacology; Psychiatry; Psychology; Pyrazoles - administration & dosage; Pyrazoles - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB2 - antagonists & inhibitors; Rodents; Taste - drug effects
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-008-1076-0

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 Δ9-tetrahydrocannabinol (Δ9-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 Δ9-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.