Influence of zopiclone, a new generation hypnotic, on the intermediate stage and paradoxical sleep in the rat

Gauthier, Pierre; Arnaud, C.; Stutzmann, Jean‐Marie; Gottesmann, Claude

doi:10.1007/s002130050221

Cited by 22 publications

(15 citation statements)

References 27 publications

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“…In contrast, the dosages of ZAL and ESZ administered in this study (also 10 mg/kg) represent the upper limit used in many animal studies [24]–[26], and constitute between 30–100 times the maximum prescribed dose for humans [23], [27]. Thus the finding that 10 mg/kg TRA impairs sleep-mediated ocular dominance plasticity - while 10 mg/kg ZAL or ESZ do not significantly affect it - strongly indicates that pathways targeted by TRA at clinically-relevant doses are specifically involved in cortical remodeling during sleep.…”

Section: Discussionmentioning

confidence: 96%

The Sedating Antidepressant Trazodone Impairs Sleep-Dependent Cortical Plasticity

et al. 2009

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BackgroundRecent findings indicate that certain classes of hypnotics that target GABAA receptors impair sleep-dependent brain plasticity. However, the effects of hypnotics acting at monoamine receptors (e.g., the antidepressant trazodone) on this process are unknown. We therefore assessed the effects of commonly-prescribed medications for the treatment of insomnia (trazodone and the non-benzodiazepine GABAA receptor agonists zaleplon and eszopiclone) in a canonical model of sleep-dependent, in vivo synaptic plasticity in the primary visual cortex (V1) known as ocular dominance plasticity.Methodology/Principal FindingsAfter a 6-h baseline period of sleep/wake polysomnographic recording, cats underwent 6 h of continuous waking combined with monocular deprivation (MD) to trigger synaptic remodeling. Cats subsequently received an i.p. injection of either vehicle, trazodone (10 mg/kg), zaleplon (10 mg/kg), or eszopiclone (1–10 mg/kg), and were allowed an 8-h period of post-MD sleep before ocular dominance plasticity was assessed. We found that while zaleplon and eszopiclone had profound effects on sleeping cortical electroencephalographic (EEG) activity, only trazodone (which did not alter EEG activity) significantly impaired sleep-dependent consolidation of ocular dominance plasticity. This was associated with deficits in both the normal depression of V1 neuronal responses to deprived-eye stimulation, and potentiation of responses to non-deprived eye stimulation, which accompany ocular dominance plasticity.Conclusions/SignificanceTaken together, our data suggest that the monoamine receptors targeted by trazodone play an important role in sleep-dependent consolidation of synaptic plasticity. They also demonstrate that changes in sleep architecture are not necessarily reliable predictors of how hypnotics affect sleep-dependent neural functions.

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Section: Discussionmentioning

confidence: 96%

The Sedating Antidepressant Trazodone Impairs Sleep-Dependent Cortical Plasticity

et al. 2009

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“…In rats, most of them also increase the IS at the expense of PS (Gandolfo et al 1994). Zolpidem and zopiclone, third-generation hypnotics, induce sleep (Stutzmann et al 1993) but decrease the IS and PS during the first hours after administration (Gottesmann et al , 1998Gauthier et al 1997a for review), Finally, even neurosteroids (or neurosteroid analogs), which also bind to the GABA A receptor complex, favor sleep (Edgar et al1997) and extend the IS (Lancel et al 1996(Lancel et al , 1997.…”

Section: Discussionmentioning

confidence: 98%

Study of a GABA c receptor antagonist on sleep-waking behavior in rats

2001

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“…For example, in adult rats, intraperitoneal administration of zopiclone in doses ranging from 2.5 to 10 mg/kg was found to decrease W, decrease latency of SWS, increase total amount of time spent in SWS, increase the latency of REM sleep, and decrease the total amount of time spent in REM sleep [34, 35, 95]. Similarly in the guinea pigs, intraperitoneal administration of 1, 3, and 10 mg/kg doses of eszopiclone were shown to decrease W and the latency of SWS and to increase the total amount of time spent in SWS [110, 111].…”

Section: Discussionmentioning

confidence: 99%

“…The doses of both drugs were 1, 3, and 10 mg/kg. These doses were predetermined based on previous studies to determine the effects of zopiclone, eszopiclone, and zolpidem on sleep-wake behavior in guinea pigs [110, 111] and rats [34, 35]. All drugs were injected i.p.…”

Section: Methodsmentioning

confidence: 99%

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Effects of eszopiclone and zolpidem on sleep–wake behavior, anxiety-like behavior and contextual memory in rats

Huang

Radadia

Macone

et al. 2010

Behavioural Brain Research

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At present, eszopiclone and zolpidem are the most commonly prescribed drugs for treating insomnia. Despite the established relationship between sleep disturbance and anxiety, it remains unknown whether targeted treatment for insomnia may affect acute anxiety. Therefore, the objective of this study was to examine the effects of three different doses (1, 3, and 10 mg/kg) of eszopiclone and zolpidem on the states of sleep and wakefulness, levels of anxiety-like behavior, and long-term contextual memory in footshock-induced anxious rats. The results of this study demonstrated that the administration of eszopiclone and zolpidem both were equally effective in attenuating footshock stressor-induced suppression of slow-wave sleep (SWS). The administration of eszopiclone at 1 mg/kg or zolpidem at 1 and 3 mg/kg doses showed a tendency for attenuating stressor-induced suppression of REM sleep. However, the REM sleep attenuating effects of these drugs disappeared when they were administered at higher doses. The administration of eszopiclone at 3 and 10 mg/kg doses and zolpidem at all three doses reduced the power of electroencephalographic theta band frequencies during wakefulness. In addition, the administration of eszopiclone at 1 and 3 mg/kg doses suppressed stressor-induced anxiety-like behavior. The administration of zolpidem at 1, 3, or 10 mg/kg doses was not effective in attenuating stressor-induced anxiety-like behavior. Contextual memory after administration of eszopiclone at 1 mg/kg dose had no effects, but was reduced significantly with increased dosage. Contextual memory after administration of zolpidem, at all three doses, was severely disrupted. The results of this study suggest that eszopiclone at a low dose could be used effectively to control anxiety and anxiety-induced insomnia.

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Influence of zopiclone, a new generation hypnotic, on the intermediate stage and paradoxical sleep in the rat

Cited by 22 publications

References 27 publications

The Sedating Antidepressant Trazodone Impairs Sleep-Dependent Cortical Plasticity

The Sedating Antidepressant Trazodone Impairs Sleep-Dependent Cortical Plasticity

Study of a GABA c receptor antagonist on sleep-waking behavior in rats

Effects of eszopiclone and zolpidem on sleep–wake behavior, anxiety-like behavior and contextual memory in rats

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