Under Statement of Work (SOW) Task 1, the Contractor shall conduct acute drug interaction studies in rodents. Specific methods to be used in these studies shall be subject to the approval of the Contracting Officer’s Representative (COR). Under SOW Task 19, the Contractor shall conduct, as directed by the COR, special in vivo or in vitro toxicology or pharmacokinetic studies, the details of which cannot be specified in advance of the contract award. Examples include modifications of the specified protocols in Tasks 1 to 18, inclusive, to allow for a more specialized evaluation of test articlesand development of a protocol with features similar to a clinical situation. The objective of these studies shall be to determine the safety of a test article in combination with cocaine or methamphetamine, an opiate or ethanol. For purposes of cost estimation only, assume that a test article to be designated by the COR will be administered by oral gavage and tested in combination with cocaine or methamphetamine (interaction article), administered by intravenous (tail vein) injection, and that the study will be conducted in two sessions. The interval between the test article and interaction article will be 2 hours. Effects on lethality, behavior (to include convulsions) and clinical observations shall be assessed. In this study there would be 12 treatment groups comprised of 10 male rats each. Animals would be observed for treatment effects at intervals for as many as 4 hours on the dosing day and once daily for 3 days thereafter. The animals would be humanely sacrificed approximately 4 days after dosing. All test article and interaction article dosing solutions shall be assayed to verify identity and concentration. NIDA requires a complete report for the study. The study shall be conducted and reported in conformance with Good Laboratory Practice (GLP) guidelines (CFR Title 21 Part 58).