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.


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.


CONCLUSIONS
Rimonabant induces a discriminative stimulus in DTA that continues to show potential for further examination of cannabinoid receptor antagonism.
Järbe
Torbjörn U C
TU
Department of Psychology, Temple University, 265-67 Weiss Hall, 1701 North 13th Street, Philadelphia, PA 19122, USA. t.jarbe@neu.edu
Li
Chen
C
Vadivel
Subramanian K
SK
Makriyannis
Alexandros
A
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001892:Camphanes / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D013759:Dronabinol / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D013649:Taste / Q000187:drug effects
D001095:Arachidonic Acids; D001892:Camphanes; D006213:Hallucinogens; D007211:Indoles; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; C088155:methanandamide; D013759:Dronabinol; D018021:Lithium Chloride; D000077285:Rimonabant; C094023:iodopravadoline