Previous studies in this and other laboratories have shown that antibody-based therapy can be useful in antagonizing the behavioral and pharmacokinetic properties of drugs of abuse, such as phencyclidine and cocaine. Therefore, the research and training in this fellowship application are designed to examine the potential use of active and passive immunization in preventing the behavioral effects and cellular neurotoxicity in a rat model of chronic methamphetamine (METH) abuse. The first set of experiments will study the consequences of immunizing rats with a METH antigen. The effectiveness of the therapy will be assessed by behavioral measures, changes in METH tissue distribution, and changes in a marker of METH-induced cellular neurotoxicity. In the second set of experiments, the pharmacokinetic and binding properties of a high affinity anti-METH monoclonal antibody will be determined in preparation for its use as a medication in the final experiments. The final studies will assess the therapeutic benefits of passive administration of a single high dose of an anti-METH monoclonal antibody in a rat model of chronic METH use. As in the active immunization studies, therapeutic success will be determined by examining a combination of METH-induced behavioral, pharmacokinetic, and cellular effects. When integrated, these studies will provide important data for the future scale-up of immunotherapy for treating human METH abuse.
