Algorithm for drug discovery

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DESCRIPTION (provided by applicant): Significant advances in our understanding of the neural mechanisms that underlie drug-taking behavior have been made, however similar advances in developing pharmacotherapeutic interventions have yet to be realized, especially in psychomotor stimulant abuse. Medications for treatment intervention in drug abuse are sorely needed. The purpose of this application is to describe what we believe to be a novel approach to discovering the psychopharmacological properties of a drug and to apply it to the study of novel therapeutic agents. Our approach uses an automated procedure for analyzing exploratory behavior in the open field. The algorithm we are developing, termed Pattern Arrays, is capable of screening a very large number of potential behavioral endpoints (>100,000) within a single session and identifying those patterns of behavior that best characterize the particular drug. A constellation of such patterns could serve as a highly specific psychopharmacological 'fingerprint' for known and novel psychoactive compounds. The objective of this proposal is to explore the capacity of the Pattern Array to characterize psychoactive drugs with a high degree of specificity. The proposal necessarily balances a developmental need to screen a diverse set of drugs with the desire to conduct a focused systematic examination of a single abused drug class. With this in mind, we will develop appropriate methodologies and a working database by investigating the behavioral 'signatures' of several abused drug classes, and then turn our attention to cocaine therapeutics. The objectives of this proposal will be realized in two specific aims. Specific Aim 1 will create a database of psychopharmacological profiles using drugs from different classes and drugs within a class that have different mechanisms of action. Specific Aim 2 will determine the algorithmically derived 'pattern profile' of potential cocaine therapeutics. In addition this aim will investigate the 'pattern profile' when the antagonist is given in combination with cocaine. Cocaine therapeutics that are in clinical trials as well as novel therapeutics such as D3 antagonists and benzotropine analogues will be investigated. The results of these experiments will serve two goals. First, it will refine the mathematical and programming requirements in the algorithm and test strengths and weakness in the Pattern Array. Second, it will establish a core database for data mining and provide a template for use in screening novel compounds with potential clinical efficacy.