Relationship between subjective effects of cocaine and dopamine transporter occupancy

N. D. Volkow, G. J. Wang, M. W. Fischman, R. W. Foltint, J. S. Fowler, N. N. Abumrad, S. Vitkun, J. Logan, S. J. Gatley, N. Pappas, Robert Hitzemann, C. E. Shea

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)827-830
Number of pages4
JournalNature
Volume386
Issue number6627
StatePublished - Apr 24 1997
Externally publishedYes

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Dopamine Plasma Membrane Transport Proteins
Cocaine
Cocaine-Related Disorders
Brain
Reward
Positron-Emission Tomography
Motivation
Volunteers
Dopamine

ASJC Scopus subject areas

  • General

Cite this

Volkow, N. D., Wang, G. J., Fischman, M. W., Foltint, R. W., Fowler, J. S., Abumrad, N. N., ... Shea, C. E. (1997). Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature, 386(6627), 827-830.

Relationship between subjective effects of cocaine and dopamine transporter occupancy. / Volkow, N. D.; Wang, G. J.; Fischman, M. W.; Foltint, R. W.; Fowler, J. S.; Abumrad, N. N.; Vitkun, S.; Logan, J.; Gatley, S. J.; Pappas, N.; Hitzemann, Robert; Shea, C. E.

In: Nature, Vol. 386, No. 6627, 24.04.1997, p. 827-830.

Research output: Contribution to journalArticle

Volkow, ND, Wang, GJ, Fischman, MW, Foltint, RW, Fowler, JS, Abumrad, NN, Vitkun, S, Logan, J, Gatley, SJ, Pappas, N, Hitzemann, R & Shea, CE 1997, 'Relationship between subjective effects of cocaine and dopamine transporter occupancy', Nature, vol. 386, no. 6627, pp. 827-830.
Volkow ND, Wang GJ, Fischman MW, Foltint RW, Fowler JS, Abumrad NN et al. Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature. 1997 Apr 24;386(6627):827-830.
Volkow, N. D. ; Wang, G. J. ; Fischman, M. W. ; Foltint, R. W. ; Fowler, J. S. ; Abumrad, N. N. ; Vitkun, S. ; Logan, J. ; Gatley, S. J. ; Pappas, N. ; Hitzemann, Robert ; Shea, C. E. / Relationship between subjective effects of cocaine and dopamine transporter occupancy. In: Nature. 1997 ; Vol. 386, No. 6627. pp. 827-830.
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