Research Focus

The focus of the Norman Laboratory is translational research to develop medications for the treatment of cocaine abuse. 

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 and the idea that reinforcement plays any significant role in maintained self-administration behavior is of limited utility.  

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. The core of our model of the maintenance phase of drug 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 satiety threshold (DST). This latter parameter is defined as the highest concentration of drug at which 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, in the Department of Pharmacology, 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.