TRAINING IN PHARMACOLOGY, TOXICOLOGY & PHARMACEUTICAL SCIENCES 2008 ASPET SUMMER UNDERGRADUATE RESEARCH FELLOWSHIP OPPORTUNITY at the UNIVERSITY OF CINCINNATI
The Department of Psychiatry, College of Medicine is pleased to offer this research project as part of the 2007 summer ASPET SURF Training Program administered by the Department of Pharmacology & Cell Biophysics.  Students interested in this project are advised to contact Professor Norman to discover more about the project, learn what your responsibilities will be during the ten-week research training program.
2008 ASPET SURF Project #:  08 – 0XX Faculty Supervisor/Mentor: Andrew B. Norman, Ph.D. Professor Department of Psychiatry College of Medicine, University of Cincinnati Email:  andrew.norman@uc.edu
Project Title: Pharmacokinetic/pharmacodynamic mechanisms regulating drug self-administration.
Research Program Description: Drug self-administration by animals is a valid model of human addictive behavior.  It has long been considered axiomatic that drugs of abuse are self-administered because of their pleasurable (hedonic or euphoric) effects, which in turn makes these drugs positively reinforcing.  Unfortunately, these assumptions result in well-known paradoxes.  The Norman laboratory has developed a quantitative pharmacological theory of self-administration behavior in which cocaine-induced responding occurs only while drug concentrations are within a specific range that we term the compulsion zone.  Therefore, animals (and presumably humans) respond because of the drug, not for the drug.  The core of our model of the maintenance phase of self-administration is the equation: T=ln(1+DU/DST)·t1/2/ln2, which defines the inter-injection intervals (T) in terms of only three parameters: the unit dose of cocaine (DU), the elimination half-life of cocaine (t1/2) and the cocaine satiety threshold (DST).  This latter parameter is defined as the highest concentration of cocaine at which cocaine self-administration occurs.  This simple model is the first to successfully define a seemingly complex behavior in terms of purely physical parameters.  This pharmacological paradigm represents a scientifically rigorous foundation for generating testable hypotheses about the biological basis of addictive behavior.  More importantly, it provides a rational basis for the development of medications for drug addiction.  To this end an active collaboration with Dr. Jim Ball (Pharmacology & Cell Biophysics )has developed a human anti-cocaine monoclonal antibody as a pharmacokinetic antagonist of cocaine, which is intended as an immunotherapy to prevent relapse in cocaine abusers.  The Norman lab is also using drug self-administration behavior as a bioassay system to measure the absolute pharmacodynamic and pharmacokinetic potencies of receptor antagonists as a basis for developing antagonist based pharmacotherapies.
ASPET SURF Project Description:  The ASPET SURF student will undertake a specific set of experiments that require understanding of the pharmacokinetic and pharmacodynamic determinants of drug-induced behavior.  The student will learn experimental design and data analysis and graphical representation.  The student will gain experience in the surgical implantation and maintenance of intravenous catheters and running drug self-administration procedures.  Agonists and antagonists of specific neurotransmitter receptors will be used to characterize the pharmacological mechanisms underlying addictive behavior.  The student will meet frequently with the mentor and the members of the research group for presentations, progress reports, and guidance.  The ASPET SURF student who makes significant research contributions will be included as a co-author of manuscripts incorporating the research results.