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

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 (BP_ND; Logan's reference tissue model with cerebellum as reference region) and volume of distribution (V_T) values were calculated in 12 and 15 grey matter brain regions, respectively. [¹⁸F]CPFPX BP_ND 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 BP_ND values were higher by 29% in females than in males. In females, sleep efficiency correlated positively and sleep latency negatively with BP_ND in most brain regions. V_T values did not differ between sexes. Sleep efficiency correlated positively with V_T 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 BP_ND 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.