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.
J. Neurochem. (2011) 116, 577–587. Abstract Considerable evidence suggests that receptor‐mediated excitation and inhibition of brainstem pedunculopontine tegmental (PPT) neurons are critically involved in the regulation of sleep–wake states. However, the molecular mechanisms operating within the PPT‐controlling sleep–wake states remain relatively unknown. This study was designed to examine sleep–wake state‐associated extracellular‐signal‐regulated kinase 1 and 2 (ERK1/2) transduction changes in the PPT of freely moving rats. The results of this study demonstrate that the levels of ERK1/2 expression, phosphorylation, and activity in the PPT increased with increased amount of time spent in sleep. The sleep‐associated increases in ERK1/2 expression, phosphorylation, and activity were not observed in the cortex, or in the immediately adjacent medial pontine reticular formation. The results of regression analyses revealed significant positive relationships between the levels of ERK1/2 expression, phosphorylation, and activity in the PPT and amounts of time spent in slow‐wave sleep, rapid eye movement sleep, and total sleep. Additionally, these regression analyses revealed significant negative relationships between the levels of ERK1/2 expression, phosphorylation, and activity in the PPT and amounts of time spent in wakefulness. Collectively, these results, for the first time, suggest that the increased ERK1/2 signaling in the PPT is associated with maintenance of sleep via suppression of wakefulness.
Anxiety is a growing public health concern that has been shown to impair both sleep and learning, and these associations have been extensively studied in recent years. In the rodent model, oftentimes various foot-shock paradigms are employed to induce stress, and subsequent sleep recordings and/or learning task results are analyzed. Previous studies have focused primarily on an individual animal’s response to stress following individual stressor exposure, thereby emulating only an isolated condition. The goal of this study was to investigate the effects of socialization on stress response, and the resultant effects on sleep architecture and aversive learning. A pair-housing/pair-exposure paradigm was utilized, and the effects of unavoidable foot-shock-induced stress on sleep architecture and aversive learning were examined. The results of the present study indicate a large, positive impact of cohabitation and shared stressful experience, as rats failed to develop sleep disturbances or learning deficits. While these results indicate the benefits and importance of companionship, the underlying mechanism of this phenomenon is yet to be elucidated.
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