Abstract
The chapter discusses the increasing dopaminergic activity of cocaine, by binding to the dopamine transporter and inhibiting dopamine uptake. The primary method by which dopamine is deactivated after its release into the synapse is also presented. Auto radiographic studies using cocaine or an analog of cocaine suggest that there are high densities of dopamine transporter labeling in dopaminergic terminal regions. The discussion on cocaine inhibition involving the re-uptake of norepinephrine and serotonin into presynaptic terminals is covered. The primary effect of cocaine is to inhibit dopamine uptake, thereby increasing extracellular dopamine, which remains available to act on pre- and postsynaptic dopamine receptors. Chronic treatment with cocaine has pronounced effects on opioid peptide levels. This chapter illustrates pretreatment with a protein kinase C inhibitor injected into the Ventral Tegmental Area (VTA) that inhibits, both the ability of cocaine to stimulate locomotor activity and the cocaine induced increase in extracellular dopamine in the nucleus accumbens. This suggests that protein kinases may be important in cocaine's effects. The studies highlight considerable evidence that the dopamine transporter and the inhibition of dopamine uptake by cocaine play a major role in the production of cocaine's effects.