HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, G.-J. Articles by Netusil, N. Search for Related Content PubMed PubMed Citation Articles by Wang, G.-J. Articles by Netusil, N.

Reproducibility of Repeated Measures of Endogenous Dopamine Competition with [¹¹C]Raclopride in the Human Brain in Response to Methylphenidate

Medical and Chemistry Departments, Brookhaven National Laboratory, Upton
Departments of Radiology and Psychiatry, State University of New York, Stony Brook
Psychiatry Service, Veterans Affairs Medical Center, Northport, New York

Correspondence: For correspondence or reprints contact: Gene-Jack Wang, MD, Medical Department, Brookhaven National Laboratory, Upton, NY 11973.

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.

Key Words: [¹¹C]raclopride • methylphenidate • pharmacologic challenge • PET • reproducibility

This article has been cited by other articles:

				N. D. Volkow, G.-J. Wang, F. Telang, J. S. Fowler, J. Logan, M. Jayne, Y. Ma, K. Pradhan, and C. Wong Profound Decreases in Dopamine Release in Striatum in Detoxified Alcoholics: Possible Orbitofrontal Involvement J. Neurosci., November 14, 2007; 27(46): 12700 - 12706. [Abstract] [Full Text] [PDF]

				T. Siessmeier, Y. Zhou, H.-G. Buchholz, C. Landvogt, I. Vernaleken, M. Piel, R. Schirrmacher, F. Rosch, M. Schreckenberger, D. F. Wong, et al. Parametric Mapping of Binding in Human Brain of D2 Receptor Ligands of Different Affinities J. Nucl. Med., June 1, 2005; 46(6): 964 - 972. [Abstract] [Full Text] [PDF]

				G.-J. Wang, L. Chang, N. D. Volkow, F. Telang, J. Logan, T. Ernst, and J. S. Fowler Decreased brain dopaminergic transporters in HIV-associated dementia patients Brain, November 1, 2004; 127(11): 2452 - 2458. [Abstract] [Full Text] [PDF]

				A. L. Brody, R. E. Olmstead, E. D. London, J. Farahi, J. H. Meyer, P. Grossman, G. S. Lee, J. Huang, E. L. Hahn, and M. A. Mandelkern Smoking-Induced Ventral Striatum Dopamine Release Am J Psychiatry, July 1, 2004; 161(7): 1211 - 1218. [Abstract] [Full Text] [PDF]

				J. C. Pruessner, F. Champagne, M. J. Meaney, and A. Dagher Dopamine Release in Response to a Psychological Stress in Humans and Its Relationship to Early Life Maternal Care: A Positron Emission Tomography Study Using [11C]Raclopride J. Neurosci., March 17, 2004; 24(11): 2825 - 2831. [Abstract] [Full Text] [PDF]

				N. D. Volkow, G.-J. Wang, J. S. Fowler, J. Logan, S. J. Gatley, C. Wong, R. Hitzemann, and N. R. Pappas Reinforcing Effects of Psychostimulants in Humans Are Associated with Increases in Brain Dopamine and Occupancy of D2 Receptors J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 409 - 415. [Abstract] [Full Text]

				N. D. Volkow, G.-J. Wang, J. S. Fowler, J. Logan, M. Gerasimov, L. Maynard, Y.-S. Ding, S. J. Gatley, A. Gifford, and D. Franceschi Therapeutic Doses of Oral Methylphenidate Significantly Increase Extracellular Dopamine in the Human Brain J. Neurosci., January 15, 2001; 21(2): RC121 - RC121. [Abstract] [Full Text] [PDF]