PET STUDIES OF BRAIN DOPAMINE IN COCAINE ABUSERS

点击翻译按钮获取中文摘要

We propose to use Positron Emission Tomography (PET) to evaluate if creased frontal metabolism in cocaine abusers is related to decreased function of presynaptic DNA neurons (PDN). We hypothesize that decreased function of PDN disrupts the activity of frontal regions modulated by the mesocortical DA system and that disruption of these frontal regions is one of the mechanisms leading to the loss of control and the drive to compulsively administer cocaine in the addicted individual. We will evaluate the function of PDN by monitoring its response to a pharmacological challenge will be methylphenidate (MP), a drug which, like cocaine, increases DA via inhibition of the DA transporter. We will measure DA release indirectly using PET to monitor the effects of MP on 11C-raclopride binding. Since endogenous DA competes with 11C-raclopride binding for the DA receptor; Inoue et, this strategy will allow us to measure relative changes in DA concentration secondary to MP. The validity and reliability of this procedure has been discussed in several recent publications. To evaluate the effects of DA changes on brain function, we will also measure the effects of MP on regional brain glucose metabolism with 2-deoxy-2[18F]fluoro-D-glucose (18FDG). The reliability and validity of the FDG test/retest design has been described elsewhere. For these studies we will recruit male and female cocaine abusers (n=20 each) and matched male and female controls (n=20 each).