AM 251 differentially effects food-maintained responding depending on food palatability.

Ligands functioning as antagonists and inverse agonists at the cannabinoid CB(1)-receptor (e.g., AM 251, AM 281, and rimonabant (previously identified as SR141716)) have been demonstrated to have effects on satiety, consumption of, and the motivation to work for, or obtain food. These represent behavioral effects that may also be linked to characteristics such as food palatability or motivation to obtain food. Given the recent removal of rimonabant from clinical trials, a thorough characterization of ingestive behaviors that are associated with other likely candidate drugs is warranted. In the present study, normal weight male Long Evans rats were trained to respond for grain or chocolate-flavored food pellets under progressive-ratio schedules of reinforcement. Rats received acute injections of the CB(1) receptor antagonist AM 251 (0.3-3.0 mg/kg) or vehicle prior to daily testing sessions. Administration of AM 251 produced significant dose-dependent reductions in responding for, deliveries of, and break points (BP) associated with chocolate-flavored but not grain pellets. These data add to the literature demonstrating the ability of CB(1) antagonists to selectively reduce motivation to obtain highly palatable reinforcers.