Modulation of cerebrospinal fluid secretion facilitated by serotonergic and noradrenergic receptors in the rat choroid plexus.

BACKGROUND: The intracranial pressure (ICP) increases at night, partly due to an elevated rate of cerebrospinal fluid (CSF) secretion, which may have therapeutic implications for pressure-related disorders. With similar diurnal regulation in nocturnal rodents and diurnal humans, the diurnally fluctuating CSF dynamics may be governed by nightly shifts in central neuromodulators. METHOD: We determined the CSF secretion rate in rats upon modulation by melatonin, serotonin, and noradrenaline in association with transcript and protein analysis of choroid plexus receptors. RESULTS: The CSF secretion rate was unaffected by melatonin administration, but was reduced with central delivery of serotonin or noradrenaline. The latter produced only a brief surge in the CSF secretion rate upon systemic delivery. The neuromodulators may thus act on the luminal side of the choroid plexus on the selection of serotonergic and adrenergic receptors expressed in this tissue, some of which displayed diurnal regulation. CONCLUSION: Diurnally fluctuating central serotonin and noradrenaline levels and/or diurnal fluctuation in choroid plexus adrenergic receptor expression may contribute to the diurnal shift in human and rodent CSF secretion rate. These signaling pathways could thus potentially be harnessed to create pharmacological modulation of the CSF secretion rate in pathological conditions of elevated ICP.