Spontaneous Eye Blink Rate (EBR) Is Uncorrelated with Dopamine D2 Receptor Availability and Unmodulated by Dopamine Agonism in Healthy Adults

eNeuro. 2017 Sep 18;4(5):ENEURO.0211-17.2017. doi: 10.1523/ENEURO.0211-17.2017. eCollection Sep-Oct 2017.

Abstract

Spontaneous eye blink rate (EBR) has been proposed as a noninvasive, inexpensive marker of dopamine functioning. Support for a relation between EBR and dopamine function comes from observations that EBR is altered in populations with dopamine dysfunction and EBR changes under a dopaminergic manipulation. However, the evidence across the literature is inconsistent and incomplete. A direct correlation between EBR and dopamine function has so far been observed only in nonhuman animals. Given significant interest in using EBR as a proxy for dopamine function, this study aimed to verify a direct association in healthy, human adults. Here we measured EBR in healthy human subjects whose dopamine D2 receptor (DRD2) availability was assessed with positron emission tomography (PET)-[18F]fallypride to examine the predictive power of EBR for DRD2 availability. Effects of the dopamine agonist bromocriptine on EBR also were examined to determine the responsiveness of EBR to dopaminergic stimulation and, in light of the hypothesized inverted-U profile of dopamine effects, the role of DRD2 availability in EBR responsivity to bromocriptine. Results from 20 subjects (age 33.6 ± 7.6 years, 9F) showed no relation between EBR and DRD2 availability. EBR also was not responsive to dopaminergic stimulation by bromocriptine, and individual differences in DRD2 availability did not modulate EBR responsivity to bromocriptine. Given that EBR is hypothesized to be particularly sensitive to DRD2 function, these findings suggest caution in using EBR as a proxy for dopamine function in healthy humans.

Keywords: PET; dopamine; eye blink rate.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Benzamides / pharmacology
  • Blinking / drug effects
  • Blinking / physiology*
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Bromocriptine / pharmacology*
  • Dopamine Agonists / pharmacology*
  • Dopamine D2 Receptor Antagonists / pharmacology
  • Double-Blind Method
  • Female
  • Healthy Volunteers
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Pyrrolidines / pharmacology
  • Receptors, Dopamine D2 / metabolism*
  • Young Adult

Substances

  • Benzamides
  • Dopamine Agonists
  • Dopamine D2 Receptor Antagonists
  • N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Bromocriptine