Effects of anti-phencyclidine and anti-(+)-methamphetamine monoclonal antibodies alone and in combination on the discrimination of phencyclidine and (+)-methamphetamine by pigeons

• Published in: Psychopharmacologia Vol. 185; no. 1; pp. 36 - 44
• Main Authors: DANIELS, J. R, WESSINGER, W. D, HARDWICK, W. C, LI, M, GUNNELL, M. G, HALL, C. J, OWENS, S. M, MCMILLAN, D. E
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.03.2006; Springer Nature B.V
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Behavior, Animal - drug effects; Biological and medical sciences; Birds; Central Nervous System Agents - pharmacology; Columbidae; Conditioning, Operant; Discrimination; Discrimination Learning; Drug addictions; Drug dosages; Experiments; Generalization (Psychology); Learning - drug effects; Male; Medical sciences; Methamphetamine; Methamphetamine - pharmacology; Monoclonal antibodies; Neuropharmacology; Pharmacology. Drug treatments; Phencyclidine - pharmacology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Reinforcement (Psychology); Toxicology; United States > US; Amphetamine derivatives; Psychotropic; Metamfetamine; Glutamate receptor; Monoclonal antibody; Antibody combinations; Phencyclidine; Piperidine derivatives; Hallucinogen; Drug of abuse; Antagonist; Aves; Drug; Drug discrimination; CNS stimulant; Pigeons; Neuroprotective agent; Sympathomimetic; Pigeon; Anti-(+)-methamphetamine monoclonal antibody; Vertebrata; Discrimination; Animal; Antibody specificity; NMDA receptor; Anti-phencyclidine monoclonal antibody
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-005-0299-6

Drug-specific monoclonal antibodies against phencyclidine (PCP) and (+)-methamphetamine [(+)-METH] should bind to these drugs to block their discriminative stimulus effects. To determine if mouse monoclonal antibodies against PCP and (+)-METH can block the discriminative stimulus effects of the drugs in pigeons. Pigeons were trained to discriminate among intramuscular injections of saline, 1 mg/kg PCP, and 2 mg/kg (+)-METH. After responding stabilized, cumulative dose-response curves were obtained for PCP and (+)-METH. Doses of an anti-PCP antibody at 620 mg/kg (anti-PCP mAb6B5) with a K (D) of 1.3 nM for PCP and no measurable affinity for (+)-METH and 1,000 mg/kg doses of anti-(+)-METH antibody (anti-METH mAb6H7) with a K (D) of 41 nM for (+)-METH and no measurable affinity for PCP were subsequently administered, first alone and later in combination after which the dose-response curves were redetermined. When the antibodies were given alone, the anti-PCP antibody blocked the discriminative stimulus effects of PCP, but not those of (+)-METH, and the anti-(+)-METH antibody blocked the discriminative stimulus effects of (+)-METH, but not those of PCP. The anti-PCP antibody shifted the PCP dose-response curve further to the right and for a longer time than the anti-(+)-METH antibody shifted the dose response curve for (+)-METH. When the anti-PCP and anti-(+)-METH antibodies were administered on the same day, the discriminative stimulus effects of both drugs were completely blocked 1 day after antibody administration. These experiments demonstrate the high specificity of the antibodies for the drugs to which they bind and show that monoclonal antibodies can be combined to antagonize the effects of more than one drug.