Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate

Gene Jack Wang, Nora D. Volkow, Joanna S. Fowler, Jean Logan, Naomi R. Pappas, Christopher T. Wong, Robert Hitzemann, Noelwah Netusil

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The measure of changes in synaptic dopamine (DA) concentration in response to the psychostimulant drug methylphenidate (MP) has been used as an indicator of responsiveness of the DA system. The purpose of this study was to assess the reproducibility of these measures. Methods: Seven healthy subjects were scanned with PET and [11C]raclopride twice in the same day: 7 min after placebo or methylphenidate (0.5 mg/kg) administration. In parallel we also measured the physiologic and behavioral responses to placebo and to methylphenidate. The same procedures were repeated 1-2 wk later to assess test-retest reproducibility. Results: Measures of plasma to brain transfer constant (K1), striatal distribution volume (DV(str)) and DA D2 receptor availability (Bmax/Kd), for the placebo condition were similar for the first (E1) and second (E2) evaluations (Bmax/Kd, E1: 2.77 ± 0.44; E2: 2.97 ± 0.44). MP administration did not change K1, but it significantly decreased DV(str) (E1: -25.9% ± 8.7%, P ≤ 0.0002; E2: -20.7% ± 11.7%, P ≤ 0.007) and Bmax/Kd (E1: -18.4% ± 8.7%, P ≤ 0.002; E2: -13.4% ± 9.2%, P ≤ 0.008), and the magnitude of these changes, though lower for E2, did not differ significantly. MP increased pulse rate(E1: +64% ± 43%, P ≤ 0.002; E2: +69% ± 33%, P ≤ 0.001), systolic pressure (E1: +37% ± 19%, P ≤ 0.0006; E2: +29% ± 15%, P ≤ 0.0009), self reports for drug effects (0: nothing to 10: extreme) of 'rush' (E1: +8 ± 3, P ≤ 0.0004; E2: +6 ± 4, P ≤ 0.01) and 'high' (E1: +8 ± 3, P ≤ 0.0001, E2: +8 ± 3, P ≤ 0.0003), anxiety (E1: +5 ± 4, P ≤ 0.02; E2: +4 ± 4, P = 0.1) and restlessness (E1: +4 ± 4, P ≤ 0.04; E2: +4 ± 5, P = 0.1). The magnitude of the cardiovascular and behavioral effects did not differ between E1 and E2. Conclusion: MP-induced changes in striatal DV and in Bmax/Kd, as well as the behavioral and cardiovascular effects, were reproducible with repeated administration.

Original languageEnglish (US)
Pages (from-to)1285-1291
Number of pages7
JournalJournal of Nuclear Medicine
Volume40
Issue number8
StatePublished - Aug 1999
Externally publishedYes

Fingerprint

Raclopride
Methylphenidate
Dopamine
Brain
Corpus Striatum
Placebos
Psychomotor Agitation
Dopamine D2 Receptors
Pharmaceutical Preparations
Self Report
Healthy Volunteers
Anxiety
Heart Rate
Blood Pressure

Keywords

  • [C]raclopride
  • Methylphenidate
  • PET
  • Pharmacologic challenge
  • Reproducibility

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Wang, G. J., Volkow, N. D., Fowler, J. S., Logan, J., Pappas, N. R., Wong, C. T., ... Netusil, N. (1999). Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate. Journal of Nuclear Medicine, 40(8), 1285-1291.

Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate. / Wang, Gene Jack; Volkow, Nora D.; Fowler, Joanna S.; Logan, Jean; Pappas, Naomi R.; Wong, Christopher T.; Hitzemann, Robert; Netusil, Noelwah.

In: Journal of Nuclear Medicine, Vol. 40, No. 8, 08.1999, p. 1285-1291.

Research output: Contribution to journalArticle

Wang, Gene Jack ; Volkow, Nora D. ; Fowler, Joanna S. ; Logan, Jean ; Pappas, Naomi R. ; Wong, Christopher T. ; Hitzemann, Robert ; Netusil, Noelwah. / Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate. In: Journal of Nuclear Medicine. 1999 ; Vol. 40, No. 8. pp. 1285-1291.
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abstract = "The measure of changes in synaptic dopamine (DA) concentration in response to the psychostimulant drug methylphenidate (MP) has been used as an indicator of responsiveness of the DA system. The purpose of this study was to assess the reproducibility of these measures. Methods: Seven healthy subjects were scanned with PET and [11C]raclopride twice in the same day: 7 min after placebo or methylphenidate (0.5 mg/kg) administration. In parallel we also measured the physiologic and behavioral responses to placebo and to methylphenidate. The same procedures were repeated 1-2 wk later to assess test-retest reproducibility. Results: Measures of plasma to brain transfer constant (K1), striatal distribution volume (DV(str)) and DA D2 receptor availability (Bmax/Kd), for the placebo condition were similar for the first (E1) and second (E2) evaluations (Bmax/Kd, E1: 2.77 ± 0.44; E2: 2.97 ± 0.44). MP administration did not change K1, but it significantly decreased DV(str) (E1: -25.9{\%} ± 8.7{\%}, P ≤ 0.0002; E2: -20.7{\%} ± 11.7{\%}, P ≤ 0.007) and Bmax/Kd (E1: -18.4{\%} ± 8.7{\%}, P ≤ 0.002; E2: -13.4{\%} ± 9.2{\%}, P ≤ 0.008), and the magnitude of these changes, though lower for E2, did not differ significantly. MP increased pulse rate(E1: +64{\%} ± 43{\%}, P ≤ 0.002; E2: +69{\%} ± 33{\%}, P ≤ 0.001), systolic pressure (E1: +37{\%} ± 19{\%}, P ≤ 0.0006; E2: +29{\%} ± 15{\%}, P ≤ 0.0009), self reports for drug effects (0: nothing to 10: extreme) of 'rush' (E1: +8 ± 3, P ≤ 0.0004; E2: +6 ± 4, P ≤ 0.01) and 'high' (E1: +8 ± 3, P ≤ 0.0001, E2: +8 ± 3, P ≤ 0.0003), anxiety (E1: +5 ± 4, P ≤ 0.02; E2: +4 ± 4, P = 0.1) and restlessness (E1: +4 ± 4, P ≤ 0.04; E2: +4 ± 5, P = 0.1). The magnitude of the cardiovascular and behavioral effects did not differ between E1 and E2. Conclusion: MP-induced changes in striatal DV and in Bmax/Kd, as well as the behavioral and cardiovascular effects, were reproducible with repeated administration.",
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AU - Wang, Gene Jack

AU - Volkow, Nora D.

AU - Fowler, Joanna S.

AU - Logan, Jean

AU - Pappas, Naomi R.

AU - Wong, Christopher T.

AU - Hitzemann, Robert

AU - Netusil, Noelwah

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N2 - The measure of changes in synaptic dopamine (DA) concentration in response to the psychostimulant drug methylphenidate (MP) has been used as an indicator of responsiveness of the DA system. The purpose of this study was to assess the reproducibility of these measures. Methods: Seven healthy subjects were scanned with PET and [11C]raclopride twice in the same day: 7 min after placebo or methylphenidate (0.5 mg/kg) administration. In parallel we also measured the physiologic and behavioral responses to placebo and to methylphenidate. The same procedures were repeated 1-2 wk later to assess test-retest reproducibility. Results: Measures of plasma to brain transfer constant (K1), striatal distribution volume (DV(str)) and DA D2 receptor availability (Bmax/Kd), for the placebo condition were similar for the first (E1) and second (E2) evaluations (Bmax/Kd, E1: 2.77 ± 0.44; E2: 2.97 ± 0.44). MP administration did not change K1, but it significantly decreased DV(str) (E1: -25.9% ± 8.7%, P ≤ 0.0002; E2: -20.7% ± 11.7%, P ≤ 0.007) and Bmax/Kd (E1: -18.4% ± 8.7%, P ≤ 0.002; E2: -13.4% ± 9.2%, P ≤ 0.008), and the magnitude of these changes, though lower for E2, did not differ significantly. MP increased pulse rate(E1: +64% ± 43%, P ≤ 0.002; E2: +69% ± 33%, P ≤ 0.001), systolic pressure (E1: +37% ± 19%, P ≤ 0.0006; E2: +29% ± 15%, P ≤ 0.0009), self reports for drug effects (0: nothing to 10: extreme) of 'rush' (E1: +8 ± 3, P ≤ 0.0004; E2: +6 ± 4, P ≤ 0.01) and 'high' (E1: +8 ± 3, P ≤ 0.0001, E2: +8 ± 3, P ≤ 0.0003), anxiety (E1: +5 ± 4, P ≤ 0.02; E2: +4 ± 4, P = 0.1) and restlessness (E1: +4 ± 4, P ≤ 0.04; E2: +4 ± 5, P = 0.1). The magnitude of the cardiovascular and behavioral effects did not differ between E1 and E2. Conclusion: MP-induced changes in striatal DV and in Bmax/Kd, as well as the behavioral and cardiovascular effects, were reproducible with repeated administration.

AB - The measure of changes in synaptic dopamine (DA) concentration in response to the psychostimulant drug methylphenidate (MP) has been used as an indicator of responsiveness of the DA system. The purpose of this study was to assess the reproducibility of these measures. Methods: Seven healthy subjects were scanned with PET and [11C]raclopride twice in the same day: 7 min after placebo or methylphenidate (0.5 mg/kg) administration. In parallel we also measured the physiologic and behavioral responses to placebo and to methylphenidate. The same procedures were repeated 1-2 wk later to assess test-retest reproducibility. Results: Measures of plasma to brain transfer constant (K1), striatal distribution volume (DV(str)) and DA D2 receptor availability (Bmax/Kd), for the placebo condition were similar for the first (E1) and second (E2) evaluations (Bmax/Kd, E1: 2.77 ± 0.44; E2: 2.97 ± 0.44). MP administration did not change K1, but it significantly decreased DV(str) (E1: -25.9% ± 8.7%, P ≤ 0.0002; E2: -20.7% ± 11.7%, P ≤ 0.007) and Bmax/Kd (E1: -18.4% ± 8.7%, P ≤ 0.002; E2: -13.4% ± 9.2%, P ≤ 0.008), and the magnitude of these changes, though lower for E2, did not differ significantly. MP increased pulse rate(E1: +64% ± 43%, P ≤ 0.002; E2: +69% ± 33%, P ≤ 0.001), systolic pressure (E1: +37% ± 19%, P ≤ 0.0006; E2: +29% ± 15%, P ≤ 0.0009), self reports for drug effects (0: nothing to 10: extreme) of 'rush' (E1: +8 ± 3, P ≤ 0.0004; E2: +6 ± 4, P ≤ 0.01) and 'high' (E1: +8 ± 3, P ≤ 0.0001, E2: +8 ± 3, P ≤ 0.0003), anxiety (E1: +5 ± 4, P ≤ 0.02; E2: +4 ± 4, P = 0.1) and restlessness (E1: +4 ± 4, P ≤ 0.04; E2: +4 ± 5, P = 0.1). The magnitude of the cardiovascular and behavioral effects did not differ between E1 and E2. Conclusion: MP-induced changes in striatal DV and in Bmax/Kd, as well as the behavioral and cardiovascular effects, were reproducible with repeated administration.

KW - [C]raclopride

KW - Methylphenidate

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KW - Pharmacologic challenge

KW - Reproducibility

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