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J Neurophysiol 92: 2198-2206, 2004. First published June 22, 2004; doi:10.1152/jn.00099.2004
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GABAA Receptors Inhibit Acetylcholine Release in Cat Pontine Reticular Formation: Implications for REM Sleep Regulation

Jacqueline Vazquez and Helen A. Baghdoyan

Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109

Submitted 2 February 2004; accepted in final form 10 June 2004

This study used in vivo microdialysis in cat (n = 12) to test the hypothesis that gamma aminobutyric acid A (GABAA) receptors in the pontine reticular formation (PRF) inhibit acetylcholine (ACh) release. Animals were anesthetized with halothane to hold arousal state constant. Six concentrations of the GABAA receptor antagonist bicuculline (0.03, 0.1, 0.3, 1, 3, and 10 mM) were delivered to a dialysis probe in the PRF, and endogenously released ACh was collected simultaneously. Bicuculline caused a concentration dependent increase in ACh release (maximal increase = 345%; EC50 = 1.3 mM; r2 = 0.997). Co-administration of the GABAA receptor agonist muscimol prevented the bicuculline-induced increase in ACh release. In a second series of experiments, the effects of bicuculline (0.1, 0.3, 1, and 3 mM) on ACh release were examined without the use of general anesthesia. States of wakefulness, rapid-eye-movement (REM) sleep, and non-REM sleep were identified polygraphically before and during dialysis delivery of bicuculline. Higher concentrations of bicuculline (1 and 3 mM) significantly increased ACh release during wakefulness (36%), completely suppressed non-REM sleep, and increased ACh release during REM sleep (143%). The finding that ACh release in the PRF is modulated by GABAA receptors is consistent with the interpretation that inhibition of GABAergic transmission in the PRF contributes to the generation of REM sleep, in part, by increasing pontine ACh release.


Address for reprint requests and other correspondence: H. A. Baghdoyan, Dept. of Anesthesiology, The University of Michigan, 7433 Medical Sciences Bldg. I, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0615 (E-mail: helenb{at}umich.edu).







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