Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain

Nora D. Volkow, Gene Jack Wang, Marian W. Fischman, Richard Foltin, Joanna S. Fowler, Dinko Franceschi, Maja Franceschi, Jean Logan, Samuel J. Gatley, Christopher Wong, Yu Shin Ding, Robert Hitzemann, Naomi Pappas

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

The route of administration influences the reinforcing effects of cocaine. Here we assessed whether there were differences in the efficacy of cocaine to block the dopamine transporters (major target for cocaine's reinforcing effects), as a function of route of administration. Positron emission tomography and [11C]cocaine, a dopamine transporter radioligand, were used to compare the levels of dopamine transporter blockade induced by intravenous, smoked and intranasal cocaine in 32 current cocaine abusers. In parallel, the temporal course for the self-reports of 'high' were obtained. Cocaine significantly blocked dopamine transporters. The levels of blockade were comparable across all routes of administration and a dose effect was observed for intravenous and intranasal cocaine but not for smoked cocaine. For equivalent levels of cocaine in plasma and DAT blockade, smoked cocaine induced significantly greater self reports of 'high' than intranasal cocaine and showed a trend for a greater effect than intravenous cocaine. The time to reach peak subjective was significantly faster for smoked (1.4 ± 0.5 min) than for intravenous cocaine (3.1 ± 0.9 min), which was faster than intranasal cocaine (14.6 ± 8 min). Differences in the reinforcing effects of cocaine as a function of the route of administration are not due to differences in the efficacy of cocaine to block the dopamine transporters. The faster time course for the subjective effects for smoked than intravenous and for intravenous than for intranasal cocaine highlights the importance of the speed of cocaine's delivery into the brain on its reinforcing effects. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)1507-1515
Number of pages9
JournalLife Sciences
Volume67
Issue number12
DOIs
StatePublished - Aug 11 2000

Keywords

  • Addiction
  • Imaging
  • PET
  • Pharmacokinetics
  • Reinforcement

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Volkow, N. D., Wang, G. J., Fischman, M. W., Foltin, R., Fowler, J. S., Franceschi, D., Franceschi, M., Logan, J., Gatley, S. J., Wong, C., Ding, Y. S., Hitzemann, R., & Pappas, N. (2000). Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain. Life Sciences, 67(12), 1507-1515. https://doi.org/10.1016/S0024-3205(00)00731-1