Dopamine transporter regulation during four nights of REM sleep deprivation followed by recovery--an in vivo molecular imaging study in humans

Abstract

Objectives: To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers.

Design: Prospective study.

Setting: Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [99mTc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity.

Patients or participants: Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived).

Measurements and results: Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation.

Conclusion: Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.

Figure 1

Schematic representation of the experimental protocol of the study.

Figure 2

Averaged brain images based on three consecutive slice regions of interest (ROIs) for [^99mTc]TRODAT-1 were used to estimate the concentration of DAT in the striatum (right and left at baseline) post-SD, and post-sleep recovery. An elliptical ROI was placed on three consecutive slices in the occipital cortex, an area used for reference of non-specific DAT binding.

Figure 3

Sleep architecture during the experimental protocol in control and sleep-deprived (SD) groups at baseline (B), during nights of SD (N1, N2, N3, N4), and during nights of sleep recovery (R1, R2, R3). The data are expressed as the mean ± SEM (n = 10 volunteers per group). *, significant differences vs. baseline; #, significant differences vs. R1; ¥, significant differences vs. the control group in each respective time-point (ANOVA for repeated measures, followed by a Tukey-Kramer test, see text for p-values). Percentage of NREM stage 2 sleep (A); percentage of sleep efficiency (B); percentage of slow wave sleep (SWS) (C); percentage of REM sleep (D); REM sleep latency in minutes(E); and SWS latency in minutes (F).