The major objectives of this contract are to establish methods for evaluating the neurotoxicity of drugs of abuse or medications which may be of potential benefit in treating drug addiction. Compounds to be evaluated for neurotoxicity will be furnished by NIDA. The neurotoxicity screen(s) resulting from this effort will incorporate sensitive neurochemical and neuroanatomical techniques that are capable of evaluating toxicity affecting monoaminergic systems and excitotoxin- induced neurotoxicity. In developing this screen, reference compounds should be used to assess the sensitivity and reliability of the techniques employed. Both rodents and primates will be used in these studies. Initial studies will be conducted in rodents, but full evaluation of test compounds will require primate studies. The initial compound that will be evaluated is ibogaine; up to two additional compounds may be evaluated during the course of this contract. A full characterization of ibogaine's neurotoxicity in both rat and primate will be obtained, including diose- effects analysis, sites of action, and, if possible, mechanism of action.
