Several Studies Indicate That Sleep Promotes Memory Consolidation in Humans1,2 and Is As- Sociated with Biochemical Events That May

1381 SEVERAL STUDIES INDICATE THAT SLEEP PROMOTES MEMORY CONSOLIDATION IN HUMANS1,2 AND IS ASSOCIATED WITH BIOCHEMICAL EVENTS THAT MAY promote synaptic plasticity,3 which is thought to be the cellular substrate of memory formation.4 However, it is not known how drugs commonly prescribed for insomnia influence these processes. For example, while it is known that hypnotics acting at the GABAA-receptor (GABAA-R) produce anterograde amnesia5 and impair daytime cognitive function6 and in vitro synaptic plasticity,7,8 only a handful of studies have examined the impact of hypnotic sleep on sleep-dependent memory formation.9,10 Considering that most hypnotic agents target the GABAA-R, which is critical in certain forms of plasticity and memory formation,6,11 it is possible that different classes of hypnotics have different effects on plastic events that normally occur during sleep. This may also be true for more recently developed hypnotics such as ramelteon, which target MT1 and MT2 melatonin receptors, because high doses of melatonin (10 mg/kg, i.p.) impair the induction of in vitro synaptic plasticity.12 In addition, hypnotics may influence sleep-dependent memory processes by altering the normal expression of sleep related genes13 or the amounts of different sleep states or cortical activity during sleep.14 Benzodiazepines (BDZ), and to a lesser extent, non-benzodiazepines (NBDZ), suppress REM sleep and NREM slow wave activity (SWA) while increasing thalamocortical spindling.14 REM sleep and spindles have in turn been hypothesized to promote different forms of memory consolidation while SWA may promote Hebbian and non-Hebbian synaptic plasticity.3,15 To determine the impact of hypnotic use on memory processes that may normally occur during sleep we examined the effects of 3 different classes of hypnotics on a canonical form of in vivo cortical plasticity. If vision is blocked in one eye (monocular deprivation, MD) during a critical period of development, the responses of most neurons in primary visual cortex (V1) shift in favor of the open eye.16 We have shown that this type of plasticity, known as ocular dominance plasticity (ODP), is consolidated by sleep and inhibited by sleep deprivation or when activity in the visual cortex is reversibly blocked during sleep.17-19 In this study, we investigated the effects of the BDZ triazolam (Tm; Halcion), the NBDZ zolpidem (Zm; Ambien) and the melatonin receptor agonist ramelteon (Rm, Rozerem) on this process.