This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A wide variety of botanical products are readily available for public purchase and consumption. While many of these products may indeed possess therapeutic effects for various legitimate medical conditions, it is also the case that an increasing number of these unregulated botanical products are consumed for recreational rather than for medical purposes. While the abuse liability of some natural products is well documented, many others have not undergone such evaluation in well-controlled scientific studies. Unlike single entity pharmaceutical products, botanicals contain a large number of diverse chemical constituents that often act synergistically to exert a given effect (Tyler, 1994). The type of extraction process utilized can have dramatic effects on the pharmacological activity of the plant product (Murray, 1992). The study of the abuse potential of botanical products requires a multidisciplinary effort consisting of expertise in ethnobotany, natural product chemistry, natural product extraction analytical chemistry, pharmacology and behavioral psychology. The ability to identify which plant constituents are associated with rewarding effects requires, an extraction/fractionation methodology that yields an array of plant extracts and fractions containing varying levels of individual constituents, an in vivo assay (e.g., place preference paradigm) capable of quantifying the rewarding properties of botanical products and a regression analysis that establishes a causal connection between the behavioral endpoints (i.e., predictor variable) and the plant constituent (i.e., criterion variable). The overall objective of this research project is to develop a standardized in vivo bioassay that can be used to screen botanical products with the goal of identifying constituents that possess rewarding properties in plants with an abuse liability. This project will utilize the expertise of natural product scientists at the National Center for Natural Products Research in providing the needed plant extracts and fractions for screening, and to subsequently identify the chemical identity of the active components. Quantification of the rewarding properties of these products will be done using the place preference paradigm. Multiple regression analyses wili identify active constituents within these plant extracts and fractions. These data will provide, in part, the necessary information to initiate controls and regulation of botanical products that may likely be harmful to consumers. In addition, these tests may help in the development of these compounds or their analogs as therapeutic agents.
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