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 language | English (US) |
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Pages (from-to) | 527-538 |
Number of pages | 12 |
Journal | Psychopharmacology |
Volume | 229 |
Issue number | 3 |
DOIs | |
State | Published - Oct 2013 |
Externally published | Yes |
Keywords
- Addiction
- Dopamine
- Gray matter
- Inhibitory control
- Methamphetamine
- Prefrontal cortex
- Striatum
ASJC Scopus subject areas
- Pharmacology