title: Monoaminergic dysfunction in recreational users of dexamphetamine.
abstract: Preclinical studies suggest that dexamphetamine (dAMPH) can lead to monoaminergic neurotoxicity. This exploratory study aimed to investigate effects of recreational dAMPH use on the dopamine (DA) and noradrenaline (NA) systems in humans. To that purpose, eight male abstinent dAMPH (26.0 ± 4.0 years) users and 10 age- and IQ-matched male healthy control subjects (23.0 ± 3.8) underwent neuropsychological testing sensitive to DAergic function and single photon emission computed tomography (SPECT) scanning with [(123)I]FP-CIT to determine striatal DA transporter (DAT) binding. In addition, changes in cerebral blood flow (CBF) induced by the DA/NA reuptake inhibitor methylphenidate (MPH) were measured using pharmacological magnetic resonance imaging (phMRI). Performance of dAMPH users was significantly worse on executive function and verbal memory tasks. Striatal DAT binding ratios were on average lower in dAMPH users (near-significant, p=0.05). In addition, CBF in control subjects decreased significantly in response to MPH in gray matter and basal ganglia, among which the striatum, thalamus and hippocampus by 10% to 29%. However, in dAMPH users the CBF response was blunted in most brain areas studied, only decreasing in the hippocampus and orbitofrontal cortex. When comparing groups, CBF response was found to be significantly different in the thalamus with a decrease for healthy controls and a blunted response in dAMPH users. Collectively, our findings of a blunted hemodynamic response in monoaminergic regions, in combination with indications for lower striatal DAT binding and poorer behavioral measures are likely to represent DAergic dysfunction in dAMPH users, although NAergic dysfunction may also play a role.
authors: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Brain Imaging Center at the Academic Medical Centre, Amsterdam, The Netherlands. Electronic address: m.l.schouw@amc.uva.nl.
authors: M L J
authors: ML
authors: Schouw
authors: M W A
authors: MW
authors: Caan
authors: H M
authors: HM
authors: Geurts
authors: B
authors: B
authors: Schmand
authors: J
authors: J
authors: Booij
authors: A J
authors: AJ
authors: Nederveen
authors: L
authors: L
authors: Reneman
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D003913:Dextroamphetamine / Q000009:adverse effects*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D055030:Drug Users / Q000523:psychology*; D056344:Executive Function / Q000187:drug effects; D059907:Functional Neuroimaging; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008568:Memory / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology; D009483:Neuropsychological Tests; D011877:Radionuclide Imaging; D014326:Tropanes
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D008774:Methylphenidate; D003913:Dextroamphetamine
keywords: Cognition; Dextroamphetamine; Dopamine; Methylphenidate; PhMRI; SPECT