Disrupted melatonin-secretion during alcohol withdrawal.

1. The synthesis of the pineal hormone, melatonin, is under adrenergic control. The brain's rhythm generating system (suprachiasmatic nucleus and associated systems) which is synchronised by the light-dark cycle controls norepinephrine release from the sympathetic nerve terminal resulting in cAMP accumulation. Increased cAMP leads to induction of the rate-limiting enzyme, N-acetyltransferase and synthesis of melatonin. The pineal exhibits a circadian rhythm with highest blood levels of the hormone being present during the night. The circadian rhythm of melatonin production provides important time-of-day and time-of-year information and, as a result, this hormonal cycle drives other 24-hour rhythms as well as seasonal cycles of reproduction, at least in photoperiodic mammals. 2. Chronic alcoholics were withdrawn from alcohol during a continued period of 4 days and nights. Blood samples were drawn from an indwelling venous catheter and sleep was monitored with polysomnography. No medication was used. No alcohol intake was allowed after admission. Bright light treatment was applied during day 3 of the study. 3. During the 4 days of alcohol-withdrawal the night time melatonin-secretion was disrupted. More than 50% of the patients had a very low secretion (< 30 pg/ml) which did not normalize during the study period. Psychopathology, sleep quality and sleep architecture improved significantly. The melatonin secretion pattern showed low values throughout the study. This low melatonin secretion might reflect the long lasting toxic influence of alcohol on the biological clock and/or a direct inhibitory effect on pineal function. These are different effects, although interrelated. 4. Ethanol has a direct inhibitory effect on pineal melatonin synthesis. A well-recognized action of ethanol is its ability to permeate and perturb the structure of cell membranes and may be related to its lipophilic properties. The changes in membrane fluidity seem to last longer than the study period of 4 days.