Request for ADAMHA Research Scientist Award. (1) Oral, schedule-induced (S-I) drug overindulgence, and chronic drug preference compared to vehicle, will be studied, especially as determined by the history of the environmental stimulus control (S/D) of preference, and current pharmacological factors. Drugs considered will be extended from cocaine to caffeine, midazolam and nicotine. Emphasis will be on tracing the situational sources initiating and maintaining drug abuse under conditions wherein pharmacologic impact is minimized, but functionally significant (oral route), while the environmental determination (S-I and S/D control) of the behavior maximized. This endeavors to clarify drug abuse initiation by an analysis of the gateways, both situational and pharmacologic, that make its acquisition probable. (2) Excessive drug intake can compromise ensuing behavioral functions. Both unconditioned behavior (e.g., locomotor activity) and psychomotor performance (e.g., fine-motor control and timing behaviors) will be measured after acute and chronic oral drug self-administration, and the resulting profiles related to a drug's measured serum concentration-time profile. (3) Results from oral self-administration will be compared to those of parenteral drug imposition.
The aim i s to predict whether serum pharmacokinetic concentration-time profiles of parent compounds and their active metabolites predict the concurrent behavior-time profiles. (4) Studies pay special attention to the behavior and kinetics of drug interactions, as concurrent use and abuse of substances, both licit and illicit, commonly occurs.
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