Methamphetamine acutely alters frontostriatal resting state functional connectivity in healthy young adults

Addict Biol. 2020 May;25(3):e12775. doi: 10.1111/adb.12775. Epub 2019 May 16.


Chronic use of methamphetamine impairs frontostriatal structure and function, which may result in increased incentive-motivational responses to drug cues and decreased regulation of drug-seeking behavior. However, less is known regarding how the drug affects these circuits after acute administration. The current study examined the effects of a single dose of methamphetamine on resting state frontostriatal functional connectivity in healthy volunteers. Participants (n = 22, 12 female) completed two sessions in which they received methamphetamine (20 mg) and placebo before a resting state scan during functional magnetic resonance imaging. Participants also provided self-report measures of euphoria and stimulation at regular intervals. We conducted seed-based voxelwise functional connectivity analyses using three bilateral striatal seed regions: nucleus accumbens (NAcc), caudate, and putamen and compared connectivity following methamphetamine versus placebo administration. Additionally, we conducted correlational analyses to assess if drug-induced changes in functional connectivity were related to changes in subjective response. Methamphetamine increased NAcc functional connectivity with medial frontal regions (ie, orbitofrontal cortex, medial frontal gyrus, and superior frontal gyrus) and decreased NAcc functional connectivity with subgenual anterior cingulate cortex (ACC). Methamphetamine also increased functional connectivity between putamen and left inferior frontal gyrus (IFG), and individuals who displayed greater drug-induced increase in connectivity reported less euphoria and stimulation. These findings provide important information regarding the effects of methamphetamine on brain function in nonaddicted individuals. Further studies will reveal whether such effects contribute to the abuse potential of the drug and whether they are related to the frontostriatal impairments observed after chronic methamphetamine use.

Keywords: fMRI; functional connectivity; healthy volunteers; methamphetamine; resting state; striatum.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / physiopathology
  • Central Nervous System Stimulants / pharmacology*
  • Female
  • Functional Neuroimaging
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / drug effects*
  • Gyrus Cinguli / physiopathology
  • Healthy Volunteers
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Methamphetamine / pharmacology*
  • Neostriatum / diagnostic imaging
  • Neostriatum / drug effects*
  • Neostriatum / physiopathology
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Nucleus Accumbens / diagnostic imaging
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / physiopathology
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiopathology
  • Putamen / diagnostic imaging
  • Putamen / drug effects
  • Putamen / physiopathology
  • Young Adult


  • Central Nervous System Stimulants
  • Methamphetamine