[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 285.16/QQ32
Topic: E.08.c. Sleep: Molecular, cellular, and pharmacology
Support: Department of Anesthesiology
Sepracor
NIH grant MH45361
NIH grant HL40881
Title: Microdialysis delivery of eszopiclone, zolpidem and diazepam to the pontine reticular
formation (PRF) of rat increases PRF acetylcholine (ACh) release
Authors: *V. S. HAMBRECHT, H. A. BAGHDOYAN, R. LYDIC;
Dept Anesthesiol, Univ. Michigan, Ann Arbor, MI
Abstract: Cholinergic and GABAergic neurotransmission in the PRF interact to regulate sleep
and wakefulness (Anesthesiology 103:1268, 2005). Administering the GABAA antagonist
bicuculline to the PRF increases PRF ACh release (J Neurophysiol 92:2198, 2004), decreases
wakefulness, and triggers rapid eye movement sleep (ibid 92:2198, 2004; ibid, 82:2015, 1999).
Increasing GABAergic transmission in the PRF increases wakefulness and decreases sleep
(Sleep 31:453, 2008). The non-benzodiazepine sedative hypnotics eszopiclone and zolpidem, as
well as the benzodiazepine diazepam enhance transmission at the GABAA receptor complex and
increase sleep. The GABAA receptor subtypes through which these drugs may alter ACh release
in the PRF have not been identified. This study is testing the hypothesis that microdialysis
delivery of eszopiclone, zolpidem, and diazepam to the PRF causes concentration-dependent
alterations in ACh release. A CMA/11 microdialysis probe was placed in the PRF of male
Sprague-Dawley rats (n=22) and PRF ACh release was measured during dialysis with Ringer‟s
(control) followed by dialysis with Ringer‟s containing either eszopiclone, zolpidem, or
diazepam (10, 100 or 1000 κM). ACh release was quantified by high performance liquid
chromatography with electrochemical detection. Repeated measures ANOVA and Tukey/Kramer
post hoc test revealed that all three drugs increased ACh release (p