High melatonin concentrations in third ventricular cerebrospinal fluid arenot due to galen vein blood recirculating through the choroid plexus

Melatonin has been implicated in several neurotropic effects, but few studi es have investigated the bioavailability of melatonin in the brain. The dis covery of periventricular sites of action adjacent to the third ventricle f orced us to investigate the dynamics of cerebrospinal fluid (CSF) melatonin release and the source of this melatonin. Our first study demonstrated une quivocally that third ventricle CSF melatonin, like jugular plasma melatoni n, accurately reflects the duration of the night and is rapidly suppressed by light. However, third ventricle CSF melatonin levels are 20-fold higher than nocturnal plasma concentrations. A further study showed that melatonin in- creased in plasma before third ventricle CSF, raising the-possibility that melatonin is taken up from the blood after recirculation through the G alen vein. However, a final experiment suggested strongly that CSF melatoni n is released directly into the third ventricle, as melatonin levels in the lateral ventricle were 7-fold lower than those in the third ventricle. Our study raises the possibility that there may be two compartments of melaton in affecting physiological functioning: the first in plasma acting on perip heral organs, and the second in the CSF affecting neurally mediated functio ns at a much higher concentration of this pineal indoleamine.