Elevation of hippocampal extracellular acetylcholine levels by methoctramine.
Previous studies suggest that m2 muscarinic receptors serve as presynaptic autoreceptors. Blocking these receptors by selective antagonists may, therefore, lead to increased acetylcholine (ACh) release. This study assessed changes in extracellular ACh levels, via in vivo microdialysis, following administration of the m2 antagonist methoctramine. Drug or placebo (Ringer's solution) was perfused via a microdialysis probe into the CA1 hippocampal region of unrestrained, awake male Fischer rats. HPLC-EC was used for online analysis of the dialysates. Methoctramine significantly enhanced ACh release in a dose-dependent fashion as compared to placebo for the doses employed (0.25-16 microM). The present in vivo data corroborate studies that show increased ACh levels in vitro following application of m2 antagonists.
Stillman
M J
MJ
Military Performance and Neuroscience Division, United States Army Research Institute of Environmental Medicine, Natick, MA 01760-5007.
Shukitt-Hale
B
B
Kong
R M
RM
Levy
A
A
Lieberman
H R
HR
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003959:Diamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D010276:Parasympatholytics / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013238:Stereotaxic Techniques; D013997:Time Factors
D003959:Diamines; D010276:Parasympatholytics; D000109:Acetylcholine; C054938:methoctramine