Exploratory Examination of the Effects of d-Amphetamine on Active-State Functional Connectivity: Influence of Impulsivity and Sensation-Seeking Status

Aaron P. Smith, Thomas H. Kelly, Joshua A. Lile, Catherine A. Martin, Miranda P. Ramirez, Michael J. Wesley

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Recent advances in diagnostic research identified that individuals with higher impulsivity and sensationseeking scores tend to report more positive subjective responses to stimulant drugs such as amphetamine. The current exploratory study hypothesized that differences in underlying mesocorticolimbic circuitry may mediate the relationship between personality and responses to stimulants due to its previously established implication in reward processes as well as the overlap between its dopaminergic projections and the pharmacodynamics of many stimulants. Forty participants (20 female) were recruited with relatively high and low-impulsivity and sensation-seeking scores as defined by the Zuckerman– Kuhlman Personality Questionnaire (Form IIIR; Zuckerman, Kuhlman, Joireman, Teta, & Kraft, 1993) for a double-blind, placebo-controlled, intranasal amphetamine administration study conducted within an MRI scanner. Active state seed-to-voxel connectivity analyses assessed the effects of amphetamine, personality, subjective responses to amphetamine, and their interactions with mesocorticolimbic seeds on data collected during monetary incentive delay and go/no-go task performance. Results indicated that amphetamine administration largely disrupted brain activity as evidenced by connectivity values shifting toward no correlation among brain stem, striatal, and frontal cortex regions. Additionally, associations of impulsivity and connectivity between ventral tegmental and medial orbitofrontal as well as lateral orbitofrontal and putamen regions were inverted from negative to positive during the placebo and amphetamine conditions, respectively. Personality was unrelated to subjective responses to amphetamine. Results are interpreted as providing evidence of underlying differences in mesocorticolimbic circuitry being a potential target for requisite diagnostic and treatment strategies implicated with stimulant use disorders, but further research is needed.

Original languageEnglish
Pages (from-to)194-208
Number of pages15
JournalExperimental and Clinical Psychopharmacology
Issue number2
StatePublished - Mar 25 2021

Bibliographical note

Publisher Copyright:
© 2021. American Psychological Association


  • Amphetamine
  • Connectivity
  • Impulsivity
  • Sensation seeking
  • Substance use

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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