Relationship between subjective effects of cocaine and dopamine transporter occupancy.
paper
Cited
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- Authors
- Volkow, N D; Wang, G J; Fischman, M W; Foltin, R W; Fowler, J S; Abumrad, N N; Vitkun, S; Logan, J; Gatley, S J; Pappas, N; Hitzemann, R; Shea, C E
- Year
- 1997
- Journal
- Nature
- PMID
- 9126740
- DOI
- 10.1038/386827a0
Cocaine is believed to work by blocking the dopamine transporter (DAT) and thereby increasing the availability of free dopamine within the brain. Although this concept is central to current cocaine research and to treatment development, a direct relationship between DAT blockade and the subjective effects of cocaine has not been demonstrated in humans. We have used positron emission tomography to determine what level of DAT occupancy is required to produce a subjective 'high' in human volunteers who regularly abuse cocaine. We report here that intravenous cocaine at doses commonly abused by humans (0.3-0.6 mg kg(-1)) blocked between 60 and 77% of DAT sites in these subjects. The magnitude of the self-reported high was correlated with the degree of DAT occupancy, and at least 47% of the transporters had to be blocked for subjects to perceive cocaine's effects. Furthermore, the time course for the high paralleled that of cocaine concentration within the striatum, a brain region implicated in the control of motivation and reward. This is the first demonstration in humans that the doses used by cocaine abusers lead to significant blockade of DAT, and that this blockade is associated with the subjective effects of cocaine. Although these findings provide justification to target the DAT for medication development they suggest that for drugs to be effective in blocking cocaine's effects they would have to be given at doses that achieve almost complete DAT occupancy.
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| Title | Year | PMID |
|---|---|---|
| The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach. | 2012 | 22358648 |
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