Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Mar 13;40(5):1172-80.
doi: 10.1038/npp.2014.301.

Dopaminergic system dysfunction in recreational dexamphetamine users

Anouk Schrantee  1 , Lena Václavů  2 , Dennis F R Heijtel  2 , Matthan W A Caan  1 , Willy Gsell  3 , Paul J Lucassen  4 , Aart J Nederveen  2 , Jan Booij  5 , Liesbeth Reneman  1
Affiliations

Dopaminergic system dysfunction in recreational dexamphetamine users

Anouk Schrantee et al. Neuropsychopharmacology. .

Abstract

Dexamphetamine (dAMPH) is a stimulant drug that is widely used recreationally as well as for the treatment of attention-deficit hyperactivity disorder (ADHD). Although animal studies have shown neurotoxic effects of dAMPH on the dopaminergic system, little is known about such effects on the human brain. Here, we studied the dopaminergic system at multiple physiological levels in recreational dAMPH users and age, gender, and IQ-matched dAMPH-naïve healthy controls. We assessed baseline D2/3 receptor availability, in addition to changes in dopamine (DA) release using single-photon emission computed tomography and DA functionality using pharmacological magnetic resonance imaging, following a dAMPH challenge. Also, the subjective responses to the challenge were determined. dAMPH users displayed significantly lower striatal DA D2/3 receptor binding compared with healthy controls. In dAMPH users, we further observed a blunted DA release and DA functionality to an acute dAMPH challenge, as well as a blunted subjective response. Finally, the lower D2/3 availability, the more pleasant the dAMPH administration was experienced by control subjects, but not by dAMPH users. Thus, in agreement with preclinical studies, we show that the recreational use of dAMPH in human subjects is associated with dopaminergic system dysfunction. These findings warrant further (longitudinal) investigations and call for caution when using this drug recreationally and for ADHD.

PubMed Disclaimer

Figures

Figure 1
Figure 1
SPECT and phMRI results. (a) Timeline of the SPECT session. (b) **Significant difference in baseline DA D2/3 receptor availability (BPND=non-displaceable binding potential) in the striatum between dAMPH users and controls (t=2.363, df=33, p=0.024). Means+SD are displayed. (c) *Significant DA release following dAMPH challenge in controls (t=3.936, df=18, p<0.01), but not in users (t=−0.704, df=15, p=0.49). **The difference between groups was significant (F=8.953, df=33, p<0.01). Means+SD are displayed. (d) Timeline of the phMRI session. (e) Percentage change of normalized striatal CBF (ssCBF) during saline administration compared with baseline for controls and users. There was no main effect of saline (F=0.858, df=34, p=0.361) and no interaction effect of time and group (F=0.087,df=34, p=0.769). Means+SD are displayed. (f) Percentage change of normalized striatal CBF (sCBF) during dAMPH administration (post2) compared with baseline for controls and users. *Significant increased ssCBF in controls (t=2.207, df=18, p=0.04) but not in users (t=−0.759, df=16, p=0.459). **The difference between groups was significant (F=4.956, df=34, p=0.03). Means+SD are displayed.
Figure 2
Figure 2
ASL time courses. (a) Grey matter ROI. Mean raw and smoothed grey matter (GM) CBF time courses for controls and users and mean heart rate (HR) for all subjects. (b) Striatal ROI. Mean raw and smoothed striatal time courses in users and controls (solid lines); specific striatal CBF (ssCBF) (dashed lines).
Figure 3
Figure 3
Correlation SPECT and phMRI. The correlation between dAMPH-induced [123I]IBZM displacement and dAMPH-induced changes in ssCBF in the striatum.
See this image and copyright information in PMC

References

    1. Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage. 2007;38:95–113. - PubMed
    1. Booij J, Korn P, Linszen DH, Royen van EA. Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography. Eur J Nucl Med. 1997;24:674–677. - PubMed
    1. Boot E, Booij J, Hasler G, Zinkstok JR, Haan de L, Linszen DH, et al. AMPT-induced monoamine depletion in humans: evaluation of two alternative [123I]IBZM SPECT procedures. Eur J Nucl Med Mol Imaging. 2008;35:1350–1356. - PMC - PubMed
    1. Brodie MS, Pesold C, Appel SB. Ethanol directly excites dopaminergic ventral tegmental area reward neurons. Alcohol Clin Exp Res. 1999;23:1848–1852. - PubMed
    1. Bruns A, Künnecke B, Risterucci C, Moreau J-L, Kienlin von M. Validation of cerebral blood perfusion imaging as a modality for quantitative pharmacological MRI in rats. Magn Reson Med. 2009;61:1451–1458. - PubMed

Publication types

MeSH terms

LinkOut - more resources