The effect of ketamine on intraspinal acetylcholine release: Involvement of spinal nicotinic receptors

The general anaesthetic ketamine affects the central cholinergic system in several manners, but its effect on spinal acetylcholine release, which may be an important transmitter in spinal antinociception, is unknown. This study aimed to investigate the effect of ketamine on spinal acetylcholine rele...

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Bibliographic Details
Published in:European journal of pharmacology 2006-03, Vol.534 (1), p.122-128
Main Authors: Abelson, Klas S.P., Goldkuhl, Renée Röstlinger, Nylund, Anders, Höglund, A. Urban
Format: Article
Language:English
Subjects:
Acetylcholine
Acetylcholine - metabolism
Anesthetics, Dissociative - pharmacology
Anesthetics, Inhalation - pharmacology
Animals
Biological and medical sciences
Bridged Bicyclo Compounds, Heterocyclic - pharmacology
Isoflurane - pharmacology
Ketamine
Ketamine - analogs & derivatives
Ketamine - pharmacology
Male
Mecamylamine - pharmacology
Medical sciences
Microdialysis
Nicotinic Agonists - pharmacology
Nicotinic Antagonists - pharmacology
Nicotinic receptor
Pharmacology. Drug treatments
Pyridines - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Nicotinic - drug effects
Spinal cord
Spinal Cord - drug effects
Spinal Cord - metabolism
Time Factors
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Summary:The general anaesthetic ketamine affects the central cholinergic system in several manners, but its effect on spinal acetylcholine release, which may be an important transmitter in spinal antinociception, is unknown. This study aimed to investigate the effect of ketamine on spinal acetylcholine release. Microdialysis probes were placed intraspinally in male rats, and acetylcholine was quantified with HPLC. Anaesthesia was switched from isoflurane (1.3%) to ketamine (150 mg/kg h), which resulted in a 500% increased acetylcholine release. The increase was attenuated during nicotinic receptor blockade (50 μM mecamylamine). The nicotinic receptor agonist epibatidine (175 μM) produced a ten-fold higher relative increase of acetylcholine release during isoflurane anaesthesia compared to ketamine anaesthesia (270% to 27%). Intraspinal administration of ketamine and norketamine both increased the acetylcholine release in high concentrations (100 μM to 10 mM). The results indicate that spinal nicotinic receptors are important for the ketamine-induced acetylcholine release, and that the effect is partly mediated at the spinal level.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2006.01.044