The nocturnal increase in human cerebrospinal fluid production is inhibited by a β₁-receptor antagonist

A circadian variation in human cerebrospinal fluid (CSF) production has recently been demonstrated using magnetic resonance phase imaging. A nightly peak in CSF production was found at ~0200, when production is approximately twice the daytime values. In the present study, we have investigated the effect of a β₁-receptor antagonist, atenolol, on the production of CSF, specifically the nocturnal production peak. CSF production was measured in fourteen healthy volunteers of both sexes in the time interval 1500-1800, with or without drug administration (100 mg orally) at 1800, and a second measurement was made in the time interval 2300-0200. In the absence of drug administration, all nine volunteers showed a significant increase in CSF production at night, from 0.34 ± 0.06 ml/min in the time interval 1500-1800 to 0.61 ± 0.05 (SE) ml/min (P < 0.005), confirming the presence of a circadian variation in these individuals. One week later, the experiment was repeated in five of these volunteers, plus an additional five volunteers, but with the administration of 100 mg atenolol orally immediately after the first measurement (at 1800). In five of the volunteers a decrease in CSF production was seen at midnight compared with daytime production values; in two volunteers CSF production remained unchanged, while three volunteers showed increased production. The average CSF production was 32% lower at night (0.27 ± 0.10 ml/min) compared with the afternoon (0.40 ± 0.07 ml/min), after administration of atenolol (P = 0.37). Analysis of the data in a 2 x 2 contingency table showed that the effect of atenolol on the nocturnal rise in CSF production was highly significant (P < 0.005). In conclusion, the present results further support the concept of a circadian variation in human CSF production and indicate that a β₁-receptor-mediated mechanism might be involved.