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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA005939-01
Application #
2862763
Study Section
Special Emphasis Panel (ZDA1-MXS-M (12))
Project Start
1999-02-01
Project End
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Byrnes-Blake, Kelly A; Laurenzana, Elizabeth M; Landes, Reid D et al. (2005) Monoclonal IgG affinity and treatment time alters antagonism of (+)-methamphetamine effects in rats. Eur J Pharmacol 521:86-94
Byrnes-Blake, Kelly A; Laurenzana, Elizabeth M; Carroll, F Ivy et al. (2003) Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats. Eur J Pharmacol 461:119-28
Laurenzana, Elizabeth M; Byrnes-Blake, Kelly A; Milesi-Halle, Alessandra et al. (2003) Use of anti-(+)-methamphetamine monoclonal antibody to significantly alter (+)-methamphetamine and (+)-amphetamine disposition in rats. Drug Metab Dispos 31:1320-6
Byrnes-Blake, K A; Carroll, F I; Abraham, P et al. (2001) Generation of anti-(+)methamphetamine antibodies is not impeded by (+)methamphetamine administration during active immunization of rats. Int Immunopharmacol 1:329-38
Riviere, G J; Byrnes, K A; Gentry, W B et al. (1999) Spontaneous locomotor activity and pharmacokinetics of intravenous methamphetamine and its metabolite amphetamine in the rat. J Pharmacol Exp Ther 291:1220-6