Individual differences in frontal cortical thickness correlate with the d-amphetamine-induced striatal dopamine response in humans.
The meso-striatal dopamine system influences responses to rewards and the motivation to seek them out. Marked individual differences in these responses are seen in laboratory animals, related in part to input from the prefrontal cortex. Here we measured the relation between cortical morphology and drug-induced striatal dopamine release in healthy young people. Participants were 24 (17 male, 7 female; age 23.0 ± 6.2 years) stimulant drug-naive subjects who underwent PET [(11)C]raclopride scans with 0.3 mg/kg d-amphetamine orally and placebo, and an anatomical MRI scan for measuring cortical thickness. As expected, d-amphetamine produced significant reductions in [(11)C]raclopride binding potential in the striatum as a percentage of the value in the placebo condition. There was substantial individual variability in this response, which was correlated with cortical thickness in the frontal lobe as a whole. The association was strongest in the anterior part of the right lateral prefrontal cortex and bilateral supplementary motor area. A thicker cortex was correlated with a smaller dopamine response. Together, this work demonstrates in humans an association between cortical thickness and the striatal dopamine response to drugs of abuse. Although prefrontal regulation of striatal function has been well studied, it was unclear whether the thickness of the prefrontal cortex was an acceptable proxy to the function of that region. These results suggest it is.
Department of Neurology & Neurosurgery, Department of Psychiatry, and Department of Psychology, McGill University, Montreal, Quebec H3A 0G4, Canada, Department of Psychiatry, University of Alberta, Edmonton, Alberta T6G 2R7, Canada, and Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec H4B 1R6, Canada.
Kevin F
KF
Casey
Mariya V
MV
Cherkasova
Kevin
K
Larcher
Alan C
AC
Evans
Glen B
GB
Baker
Alain
A
Dagher
Chawki
C
Benkelfat
Marco
M
Leyton
D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007206:Individuality; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D020891:Raclopride / Q000493:pharmacokinetics; D013223:Statistics as Topic; D055815:Young Adult
D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D020891:Raclopride; D003913:Dextroamphetamine; D004298:Dopamine