Reserpine and sleep

Abstract

Recent studies of the effects of reserpine on human sleep have reported increased rapid eye movement (REM) sleep, and decreased slow-wave (SW) sleep. These results are relevant to theories linking serotonin and the catecholamines to the control of different stages of sleep. However, since reserpine causes release and subsequent depletion of both monoamines, it is difficult to relate changes in sleep profiles to specific alterations in one or the other amine system. The results to be reported here, when compared to those obtained with other treatments which affect the biogenic amines, encourage the view that level and turnover of serotonin are the primary mediators for reserpine-induced modifications of sleep. In two separate experiments, EEG sleep patterns from 20 male Ss were examined following single and repeated oral doses (1 mg) of reserpine. In the single-dose study, reserpine caused increased REM, and decreased SW sleep, effects which became statistically significant on the post-medication (P-M) recovery session. These changes were accompanied by reduced frequency per minute of sigma spindles (stage 2) decreased eye-movement density (stage REM) and a tendency toward increased brief arousals, especially during stage REM. Examination of parameters of the REM cycle revealed that the potentiation of REM sleep was due to its reduced latency of onset, and more frequent cyclic occurrence, not to increased duration of REM episodes. The results of the repeated-dose study replicated and amplified those of the first experiment, showing that medication caused a progressive increase in the amount of stage REM, accompanied by a simultaneous loss of SW sleep. The increase in REM was again due to acceleration of its cycle rather than lengthening of its episodes. During medication, epochs of stage REM were increasingly interrupted by brief arousals, with a simulteneous decline in the density of rapid eye movements. Most of these reserpine effects persisted into the P-M recovery session.

The acceleration of the REM cycle, loss of SW sleep, decrease in sigma spindles and increase in brief arousals indicate that the acute effects of reserpine on human sleep are in the direction of activation, and the persistence of most of these alterations into the P-M session implies that they are due to depletion of one or both monoamines. However, comparison of reserpine effects on sleep with those induced by precursors and blockers of serotonin, and by monoamine oxidase inhibitors suggests that the loss of SW sleep may have resulted from depletion of serotonin, whereas acceleration of the REM cycle may have been caused by a compensatory increase in its rate of synthesis.