Dopamine release in the nucleus accumbens (N ACC) has been shown to primarily mediate the reinforcing effects of cocaine and amphetamine. Using in vivo microdialysis procedures the proposed work is designed to quantify the extracellular concentration of dopamine (DA) in the N ACC during intravenous drug self- administration. The proposed project consists of two self- administration studies. The first study is designed to quantify DA concentrations maintained during self-administration of three doses of cocaine (0.25, 0.5 and 0.75 mg/inj).
The aim of the study is to determine if the animals which self-administer different doses of cocaine will maintain DA concentrations at similar or different levels.
The aim of the second study is to compare levels of DA maintained during cocaine, amphetamine and morphine self-administration. The second study will provide detailed information about the effects of a variety of abused upon the concentration of DA in the N ACC. As would be expected, administration of a drug which blocks the reuptake of DA (i.e., cocaine) should increases the extracellular concentration of DA. Furthermore, the administration of cocaine in short regular intervals should maintain the concentration of DA at some level above basal values. The emphasis of the proposed work is not to demonstrate that the above occurs. The major aim of the proposed projects is to quantify the concentration of DA in the N ACC that animals maintain over time during cocaine self-administration. Once the threshold level at which the DA concentration stabilizes during cocaine self-administration is quantified the information can be compared to DA levels maintained during amphetamine and morphine self-administration. These experiments will provide detailed information about the actions of a variety of abused drugs upon the concentration of DA in the nucleus accumbens. Future research can use this information to assess the effects of dependence, experience, withdrawal, tolerance, and also acquisition of drug self-administration. Moreover, the effectiveness of pharmacologial methods used to treat patients who abuse drugs can be evaluated. Quantification of DA thresholds in the nucleus accumbens during self-administration has the potential to provide immediate information and can be used to direct future studies.
