title: Methamphetamine-induced increases in putamen gray matter associate with inhibitory control.
abstract: BACKGROUND
  Problematic drug use is associated with difficulty in exerting self-control over behaviors, and this difficulty may be a consequence of atypical morphometric characteristics that are exhibited by drug-experienced individuals. The extent to which these structural abnormalities result from drug use or reflect neurobiological risk factors that predate drug use, however, is unknown.
  
  
  OBJECTIVE
  The purpose of this study is to determine how methamphetamine affects corticostriatal structure and how drug-induced changes relate to alterations in inhibitory control.
  
  
  METHODS
  Structural magnetic resonance images and positron emission tomography (PET) scans, assessing dopamine D₂-like receptor and transporter availability, were acquired in monkeys trained to acquire, retain, and reverse three-choice visual discrimination problems before and after exposure to an escalating dose regimen of methamphetamine (or saline, as a control). Voxel-based morphometry was used to compare changes in corticostriatal gray matter between methamphetamine- and saline-exposed monkeys. The change in gray matter before and after the dosing regimen was compared to the change in the behavioral performance and in dopaminergic markers measured with PET.
  
  
  RESULTS
  Methamphetamine exposure, compared to saline, increased gray matter within the right putamen. These changes were positively correlated with changes in performance of methamphetamine-exposed monkeys in the reversal phase, and were negatively correlated with alterations in D₂-like receptor and DAT availability.
  
  
  CONCLUSIONS
  The results provide the first evidence that exposure to a methamphetamine dosing regimen that resembles human use alters the structural integrity of the striatum and that gray-matter abnormalities detected in human methamphetamine users are due, at least in part, to the pharmacological effects of drug experience.
authors.affiliation: Department of Psychology, UCLA Department of Psychology, PO Box 951563, Los Angeles, CA, 90095-1563, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Groman
authors.forename: Angelica M
authors.initials: AM
authors.lastname: Morales
authors.forename: Buyean
authors.initials: B
authors.lastname: Lee
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
authors.forename: James David
authors.initials: JD
authors.lastname: Jentsch
mesh_terms: D019969:Amphetamine-Related Disorders / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D000818:Animals; D002522:Chlorocebus aethiops; D003071:Cognition / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012153:Retention, Psychology / Q000187:drug effects; D012193:Reversal Learning / Q000187:drug effects; D013997:Time Factors
chemical_list: D017448:Receptors, Dopamine D2; D008694:Methamphetamine