Methamphetamine-induced increases in putamen gray matter associate with inhibitory control

Stephanie M. Groman, Angelica M. Morales, Buyean Lee, Edythe D. London, James David Jentsch

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Rationale: 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. Objectives: 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.

Original languageEnglish (US)
Pages (from-to)527-538
Number of pages12
JournalPsychopharmacology
Volume229
Issue number3
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • Addiction
  • Dopamine
  • Gray matter
  • Inhibitory control
  • Methamphetamine
  • Prefrontal cortex
  • Striatum

ASJC Scopus subject areas

  • Pharmacology

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