Cerebral A1 adenosine receptor availability in female and male participants and its relationship to sleep

Neuroimage. 2021 Dec 15:245:118695. doi: 10.1016/j.neuroimage.2021.118695. Epub 2021 Oct 31.


The neuromodulator adenosine and its receptors are mediators of sleep-wake regulation which is known to differ between sexes. We, therefore, investigated sex differences in A1 adenosine receptor (A1AR) availability in healthy human subjects under well-rested conditions using [18F]CPFPX and positron emission tomography (PET). [18F]CPFPX PET scans were acquired in 50 healthy human participants (20 females; mean age ± SD 28.0 ± 5.3 years). Mean binding potential (BPND; Logan's reference tissue model with cerebellum as reference region) and volume of distribution (VT) values were calculated in 12 and 15 grey matter brain regions, respectively. [18F]CPFPX BPND was higher in females compared to males in all investigated brain regions (p < 0.025). The largest differences were found in the pallidum and anterior cingulate cortex, where mean BPND values were higher by 29% in females than in males. In females, sleep efficiency correlated positively and sleep latency negatively with BPND in most brain regions. VT values did not differ between sexes. Sleep efficiency correlated positively with VT in most brain regions in female participants. In conclusion, our analysis gives a first indication for potential sex differences in A1AR availability even under well-rested conditions. A1AR availability as measured by [18F]CPFPX BPND is higher in females compared to males. Considering the involvement of adenosine in sleep-wake control, this finding might partially explain the known sex differences in sleep efficiency and sleep latency.

Keywords: A1AR; Adenosine receptors; PET; Sex differences; Sleep; [18F]CPFPX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Mapping / methods*
  • Female
  • Fluorodeoxyglucose F18
  • Healthy Volunteers
  • Humans
  • Male
  • Positron-Emission Tomography*
  • Radiopharmaceuticals
  • Receptor, Adenosine A1 / metabolism*
  • Sex Factors
  • Sleep*


  • Radiopharmaceuticals
  • Receptor, Adenosine A1
  • Fluorodeoxyglucose F18