Electrophysiologic and antiarrhythmic effects of AZD1305 in canine pulmonary vein sleeves. (65/173)

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AZD1305 exerts atrial predominant electrophysiological actions and is effective in suppressing atrial fibrillation and preventing its reinduction in the dog. (66/173)

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Hippocampal adult neurogenesis is enhanced by chronic eszopiclone treatment in rats. (67/173)

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Insomnia severity is an indicator of suicidal ideation during a depression clinical trial. (68/173)

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Activity of chequerboard combinations of ceftaroline and NXL104 versus beta-lactamase-producing Enterobacteriaceae. (69/173)

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Therapeutic efficacy of azaindole-1 in experimental pulmonary hypertension. (70/173)

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Treatment of insomnia in Parkinson's disease: a controlled trial of eszopiclone and placebo. (71/173)

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Benzodiazepine receptor agonists cause drug-specific and state-specific alterations in EEG power and acetylcholine release in rat pontine reticular formation. (72/173)

STUDY OBJECTIVES: Benzodiazepine (BDZ) and non-benzodiazepine (NBDZ) hypnotics enhance GABAergic transmission and are widely used for the treatment of insomnia. In the pontine reticular formation (PRF), GABA inhibits rapid eye movement (REM) sleep and acetylcholine (ACh) release. No previous studies have characterized the effects of BDZ and NBDZ hypnotics on ACh release in the PRF. This study tested 2 hypotheses: (1) that microdialysis delivery of zolpidem, eszopiclone, and diazepam to rat PRF alters ACh release in PRF and electroencephalographic (EEG) delta power and (2) that intravenous (i.v.) administration of eszopiclone to non-anesthetized rat alters ACh release in the PRF, sleep, and EEG delta power. DESIGN: A within- and between-groups experimental design. SETTING: University of Michigan. PATIENTS OR PARTICIPANTS: Adult male Crl:CD*(SD) (Sprague-Dawley) rats (n = 57). INTERVENTIONS: In vivo microdialysis of the PRF in rats anesthetized with isoflurane was used to derive the concentration-response effects of zolpidem, eszopiclone, and diazepam on ACh release. Chronically instrumented rats were used to quantify the effects of eszopiclone (3 mg/kg, i.v.) on ACh release in the PRF, sleep-wake states, and cortical EEG power. MEASUREMENTS AND RESULTS: ACh release was significantly increased by microdialysis delivery to the PRF of zolpidem and eszopiclone but not diazepam. EEG delta power was increased by zolpidem and diazepam but not by eszopiclone administered to the PRF. Eszopiclone (i.v.) decreased ACh release in the PRF of both anesthetized and non-anesthetized rats. Eszopiclone (i.v.) prevented REM sleep and increased EEG delta power. CONCLUSION: The concentration-response data provide the first functional evidence that multiple GABA(A) receptor subtypes are present in rat PRF. Intravenously administered eszopiclone prevented REM sleep, decreased ACh release in the PRF, and increased EEG delta power. The effects of eszopiclone are consistent with evidence that ACh release in the PRF is lower during NREM sleep than during REM sleep, and with data showing that cholinergic stimulation of the PRF activates the cortical EEG.  (+info)