This application is for a research scientist award that will continue to maximize efforts that can be expended in studies of the biological basis of drug abuse. Addictive disorders result from the excessive use of reinforcers. Identification and characterization of the neurobiological substrates of reinforcement is necessary for understanding the biological basis of these disorders. Four NIDA funded research projects are in progress or will be at the time of this award that directly address investigations of the mechanisms of cocaine, heroin and speedball reinforcement. It is generally accepted that DA is the mediator of the reinforcing effects of environmental events including drug and non-drug reinforcers. However, it is clear that a number of neuronal systems and brain loci are important to the processes underlying the compulsive use of drugs. The goal of this research proposal is the continued investigation of several neuronal systems involved in the self-administration of cocaine, heroin and speedball using neurotransmitter turnover rates, intracranial agonist and antagonist administration, neurotoxin lesions and microdialysis. In addition, the potential role of autoantibodies to neurotransmitter receptors in this abuse will also be investigated. This research will hopefully result in a greater understanding of the neurobiology of cocaine, heroin and speedball abuse and assist in the identification of novel treatment approaches. The past funding has permitted the candidate to spend significant effort on drug abuse research. This award has assisted in the candidate's ability to obtain salary support for hiring junior faculty that assumed major percentages of the teaching, administrative and service responsibilities that the applicant encountered. In addition, the released funds have been instrumental in obtaining support for an administrative secretary and administrative manager that assumed much of the time intensive day to day duties in the department to permit the applicant to concentrate more effectively on research and research administration. In summary, this award has made it possible for the applicant to devote significant time to research in the area of the neurobiological mechanisms of drug reinforcement.