RT Journal Article
SR Electronic
T1 Effects of Microdialyzed Oxotremorine, Carbachol, Epibatidine, and Scopolamine on Intraspinal Release of Acetylcholine in the Rat
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 100
OP 104
VO 295
IS 1
A1 Höglund, A. Urban
A1 Hamilton, Charlotte
A1 Lindblom, Lars
YR 2000
UL http://jpet.aspetjournals.org/content/295/1/100.abstract
AB Intrathecally administered cholinergic agonists such as oxotremorine (muscarinic), carbachol (mixed nicotinic and muscarinic agonist), and epibatidine (nicotinic) have all been shown to reduce nociception in behavioral studies. Thus, there is substantial evidence for a role of acetylcholine (ACh) in the control of nociception in the spinal cord, but the mechanisms regulating ACh release are not known. The present study was initiated to establish a rat model to study which mechanisms are involved in the control of ACh release. Spinal microdialysis probes were inserted intraspinally at the C1–C5 spinal level in isoflurane-anesthetized rats. The probes were perfused with Ringer's solution containing 10 μM neostigmine to prevent degradation of ACh. Oxotremorine, carbachol, epibatidine, and scopolamine, dissolved in Ringer's solution, were administered intraspinally via dialysis and 30 μl/10-min samples of dialysate were collected for HPLC analysis of ACh content. The release of ACh was found to be constant in the control (Ringer's only) situation during the experimental period of 150 min. Oxotremorine (100–1000 μM), carbachol (1 mM), and epibatidine (50–5000 μM) enhanced but scopolamine (50–200 nM) decreased the intraspinal release of ACh. Oxotremorine (ED50 = 118 μM) and epibatidine (ED50 = 175 μM) were found to produce a dose-dependent increase of ACh release. Cholinergic agonists caused an increase of intraspinal ACh and the antagonist scopolamine caused a decreased release of ACh. The data do not support an autoreceptor function of either nicotinic or muscarinic receptors in the spinal cord, contrary to what has been observed in the brain. The American Society for Pharmacology and Experimental Therapeutics