Rationale: Cannabinoid CB1 antagonists/inverse agonists suppress food-motivated behaviors and are being evaluated as potential appetite suppressants. It has been suggested that the effects of CB1 antagonism on food motivation could be related to actions on mesolimbic dopamine (DA). If this were true, then the effects of interference with cannabinoid CB1 transmission should closely resemble the effects of interference with DA transmission.
Objective: To directly compare the effects of DA antagonists with those of CB1 antagonists/inverse agonists, the present studies employed a concurrent lever-pressing/chow-intake procedure. With this task, interference with DA transmission shifts choice behavior such that lever pressing for a preferred food is decreased but chow intake is increased.
Results: Rats treated with IP injections of the DA D1 antagonist SCH39166 (ecopipam; 0.05-0.2 mg/kg) or the D2 antagonist eticlopride (0.025-0.1 mg/kg) showed substantial decreases in lever pressing and concomitant increases in chow consumption. In contrast, IP administration of the CB1 neutral antagonist AM4113 (4.0-16.0 mg/kg) or the CB1 antagonist/inverse agonist AM251 (2.0-8.0 mg/kg) decreased operant responding for pellets, but there was no corresponding increase in chow intake.
Conclusions: These effects of CB1 antagonists/inverse agonists were similar to those produced by the appetite suppressant fenfluramine and by prefeeding. In contrast, low doses of DA antagonists leave primary food motivation intact, but shift behaviors toward food reinforcers that can be obtained with lower response costs. These results suggest that the effects of interference with CB1 transmission are readily distinguishable from those of reduced DA transmission.