Acetylcholine release in the pontine reticular formation of C57BL/6J mouse is modulated by non-M1 muscarinic receptors

• Published in: Neuroscience 2004, Vol.126 (4), p.831-838
• Main Authors: Coleman, C.G., Lydic, R., Baghdoyan, H.A.
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; Analysis of Variance; Animals; arousal; B6 mouse; Bethanechol - pharmacology; Biological and medical sciences; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Male; Mice; Mice, Inbred C57BL; microdialysis; Microdialysis - methods; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; phenotyping; Receptors, Muscarinic - classification; Receptors, Muscarinic - physiology; Reticular Formation - drug effects; Reticular Formation - secretion; sleep; Sleep. Vigilance; Tetrodotoxin - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2004.04.045

Pontine acetylcholine (ACh) contributes to the regulation of electroencephalographic and behavioral arousal in all mammals so far investigated. The mouse is recognized as a powerful model for pharmacogenomics but the synaptic mechanisms regulating ACh release in mouse pontine reticular formation have not been characterized. Drug delivery by microdialysis was used in isoflurane-anesthetized C57BL/6J (B6) mice ( n=33) to test the hypothesis that muscarinic autoreceptors modulate ACh release in the pontine reticular nucleus, oral part (PnO). Dialysis delivery of tetrodotoxin to the PnO significantly decreased ACh by 58% below control levels, confirming that measured ACh reflected neurotransmitter release. The muscarinic antagonist scopolamine increased ACh release in the PnO by 21% (3 nM), 48% (10 nM), 56% (30 nM), and 104% (100 nM). The muscarinic agonist bethanechol dialyzed into the PnO significantly decreased ACh release by 60% compared with control. Dialysis delivery of relatively subtype selective muscarinic antagonists to the PnO revealed the following order of potency for increasing ACh release: scopolamine (3 nM)>AF-DX 116 (100 nM)=pirenzepine (100 nM). These data support the conclusion that ACh release in PnO of B6 mouse is modulated by non-M1 muscarinic receptors.