Acetylcholine release in the pontine reticular formation of C57BL/6J mouse is modulated by non-M1 muscarinic receptors.
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.
Coleman
C G
CG
Departments of Anesthesiology and Pharmacology, University of Michigan, 7433 Medical Sciences Building I, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0615, USA.
Lydic
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R
Baghdoyan
H A
HA
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis / Q000379:methods; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000145:classification / Q000502:physiology*; D012154:Reticular Formation / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D018723:Bethanechol; D013779:Tetrodotoxin; D000109:Acetylcholine