, Volume 236, Issue 2, pp 581–590 | Cite as

Lack of consistent sex differences in d-amphetamine-induced dopamine release measured with [18F]fallypride PET

  • Christopher T. SmithEmail author
  • Linh C. Dang
  • Leah L. Burgess
  • Scott F. Perkins
  • M. Danica San Juan
  • Darcy K. Smith
  • Ronald L. Cowan
  • Nam T. Le
  • Robert M. Kessler
  • Gregory R. Samanez-Larkin
  • David H. Zald
Original Investigation



Sex differences in the dopaminergic response to psychostimulants could have implications for drug abuse risk and other psychopathology involving the dopamine system, but human data are limited and mixed.


Here, we sought to investigate sex differences in dopamine release after oral d-amphetamine administration.


We used [18F]fallypride positron emission tomography (PET) to measure the change in dopamine D2/3 receptor availability (%ΔBPND, an index of dopamine release) between placebo and d-amphetamine sessions in two independent datasets containing a total of 39 females (on either hormonal birth control n = 18, postmenopausal n = 10, or studied in the first 10 days of their menstrual cycle n = 11) and 37 males.


Using both a priori anatomical regions of interest based on previous findings and voxelwise analyses, we failed to consistently detect broad sex differences in d-amphetamine-induced dopamine release. Nevertheless, there was limited evidence for greater right ventral striatal dopamine release in young adult males relative to similarly aged females, but this was not consistently observed across samples. Plasma estradiol did not correlate with dopamine release and this measure did not differ in females on and off hormonal birth control.


While our finding in young adults from one dataset of greater %ΔBPND in males is partially consistent with a previously published study on sex differences in d-amphetamine-induced dopamine release, our data do not support the presence of consistent widespread sex differences in this measure of dopamine release.


(up to 10): Sex differences Dopamine PET D2/3 receptor availability Dopamine release d-amphetamine 



This work was supported by AG043458 (DHZ & GRS-L) and AG042596 (GRS-L) from the National Institute on Aging and DA019670 (DHZ), DA041157 (CTS), and DA036979 (LCD) from the National Institute on Drug Abuse.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

Supplementary material

213_2018_5083_MOESM1_ESM.docx (941 kb)
ESM 1 (DOCX 941 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Christopher T. Smith
    • 1
    Email author
  • Linh C. Dang
    • 1
  • Leah L. Burgess
    • 1
  • Scott F. Perkins
    • 1
  • M. Danica San Juan
    • 1
  • Darcy K. Smith
    • 1
  • Ronald L. Cowan
    • 1
    • 2
    • 3
  • Nam T. Le
    • 3
  • Robert M. Kessler
    • 4
  • Gregory R. Samanez-Larkin
    • 5
  • David H. Zald
    • 1
    • 2
  1. 1.Department of Psychology, PMB 407817Vanderbilt UniversityNashvilleUSA
  2. 2.Department of Psychiatry and Behavioral SciencesVanderbilt University Medical CenterNashvilleUSA
  3. 3.Department of Radiology and Radiological Sciences, Medical Center NorthVanderbilt University Medical CenterNashvilleUSA
  4. 4.Department of RadiologyUAB School of MedicineBirminghamUSA
  5. 5.Department of Psychology and NeuroscienceDuke UniversityDurhamUSA

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