Pharmacokinetic antagonism of (+)-methamphetamine discrimination by a low-affinity monoclonal anti-methamphetamine antibody

Animals were trained to discriminate 5 or 10 mg/kg cocaine (rats), or 3 mg/kg (+)-amphetamine (pigeons) from saline, after which dose-response curves were determined for (+)-methamphetamine and other drugs before and after administration of a (+)-methamphetamine-specific monoclonal antibody (K(D) =250 nM). In rats trained to discriminate 10 mg/kg cocaine from saline, intravenous (+)-methamphetamine was about three times more potent as a discriminative stimulus than intraperitoneal (+)-methamphetamine. Also in these rats, intraperitoneal (+)-methamphetamine and (+)-amphetamine were about equipotent as discriminative stimuli, and were about three times more potent than intraperitoneal cocaine. In pigeons trained to discriminate 3 mg/kg intramuscular (i.m.) (+)-amphetamine from saline, (+)-methamphetamine and (+)-amphetamine were nearly equipotent, while cocaine was slightly less potent. In rats trained to discriminate 5 or 10 mg/kg cocaine from saline, intravenous administration of 1 g/kg of the antibody shifted both intravenous and intraperitoneal dose-response curves for (+)-methamphetamine discrimination approximately threefold to the right at 1 or 4 days after administration of the antibody. In pigeons trained to discriminate 3 mg/kg intramuscular (+)-amphetamine from saline, a similar shift of the (+)-methamphetamine dose-response curve to the right also lasted for 4-7 days. However, the antibody did not affect the (+)-amphetamine dose-response curve (pigeons), or the cocaine (rats) dose-response curve. The data show that a low affinity anti-(+)-methamphetamine-specific antibody can produce a specific antagonism of an effect of (+)-methamphetamine that is closely associated with its abuse.