GABAAReceptors in the Pontine Reticular Formation of C57BL/6J Mouse Modulate Neurochemical, Electrographic, and Behavioral Phenotypes of Wakefulness

Autor: Helen A. Baghdoyan, RaShonda R. Flint, Theresa Chang, Ralph Lydic
Rok vydání: 2010
Předmět:
Zdroj: The Journal of Neuroscience. 30:12301-12309
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.1119-10.2010
Popis: Drugs that potentiate transmission at GABAAreceptors are widely used to enhance sleep and to cause general anesthesia. The mechanisms underlying these effects are unknown. This study tested the hypothesis that GABAAreceptors in the pontine reticular nucleus, oral part (PnO) of mouse modulate five phenotypes of arousal: sleep and wakefulness, cortical electroencephalogram (EEG) activity, acetylcholine (ACh) release in the PnO, breathing, and recovery time from general anesthesia. Microinjections into the PnO of saline (vehicle control), the GABAAreceptor agonist muscimol, muscimol with the GABAAreceptor antagonist bicuculline, and bicuculline alone were performed in male C57BL/6J mice (n= 33) implanted with EEG recording electrodes. Muscimol caused a significant increase in wakefulness and decrease in rapid eye movement (REM) and non-REM (NREM) sleep. These effects were reversed by coadministration of bicuculline. Bicuculline administered alone caused a significant decrease in wakefulness and increase in NREM sleep and REM sleep. Muscimol significantly increased EEG power in the delta range (0.5–4 Hz) during wakefulness and in the theta range (4–9 Hz) during REM sleep. Dialysis delivery of bicuculline to the PnO of male mice (n= 18) anesthetized with isoflurane significantly increased ACh release in the PnO, decreased breathing rate, and increased anesthesia recovery time. All drug effects were concentration dependent. The effects on phenotypes of arousal support the conclusion that GABAAreceptors in the PnO promote wakefulness and suggest that increasing GABAergic transmission in the PnO may be one mechanism underlying the phenomenon of paradoxical behavioral activation by some benzodiazepines.
Databáze: OpenAIRE
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