Dopaminergic system dysfunction in recreational dexamphetamine users.
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.
1] Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands [2] Brain Imaging Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Anouk
A
Schrantee
Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Lena
L
Václavů
Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Dennis F R
DF
Heijtel
1] Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands [2] Brain Imaging Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Matthan W A
MW
Caan
MRI Department, Maccine, Singapore, Singapore.
Willy
W
Gsell
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
Paul J
PJ
Lucassen
Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Aart J
AJ
Nederveen
Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Jan
J
Booij
1] Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands [2] Brain Imaging Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Liesbeth
L
Reneman
D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D001931:Brain Mapping; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D013287:Illicit Drugs / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
D000697:Central Nervous System Stimulants; D013287:Illicit Drugs; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D003913:Dextroamphetamine; D004298:Dopamine