Effects of benzodiazepines, sleep and sleep deprivation on vigilance and memory.

Anterograde amnesia is one of the troublesome adverse effects of the benzodiazepines, especially when they are used as tranquillizers. Interestingly, benzodiazepines also produce retrograde facilitation. In this review, a unifying hypothesis concerning both the cognitive enhancement and the cognitive decrement is discussed: the decrease in vigilance or sedative-hypnotic properties of the benzodiazepines induces a superficial type of encoding and consolidation. This is expressed in anterograde amnesia. The shallower encoding also causes less retrograde interference and retrograde facilitation is the result. In this way also the positive effect of sleep on memory is explained. In a series of experiments, this hypothesis was investigated. Anterograde amnesia and retrograde facilitation was demonstrated after benzodiazepine intake in healthy, volunteers. It was striking that amnestic effects and retrograde facilitation were most prominent when memory was tested one week after drug intake. A decrease in vigilance was also obtained by sleep deprivation and an increase by the gavage of the central stimulant methylphenidate. The latter vigilance increasing drug did not change memory aspects. Also memory effects were hardly present in sleep deprived subjects with low levels of vigilance and the performance on memory tests were not changed. This jeopardizes the vigilance hypothesis of the memory effects of the benzodiazepines. However, amnesia under the influence of benzodiazepines was less for semantic related words than for unrelated words. This suggests that information might be stored without appropriate contextual cues. Only under special circumstances this information can be retrieved. It is further speculated that this storage costs less efforts leading to less retrograde interference and consequently retrograde facilitation.