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 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 microM mecamylamine). The nicotinic receptor agonist epibatidine (175 microM) 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 microM 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.
Abelson
Klas S P
KS
Division of Comparative Medicine, Department of Neuroscience, Uppsala University, BMC, Box 572, S-751 23 Uppsala, Sweden. klas.abelson@neuro.uu.se
Goldkuhl
Renée Röstlinger
RR
Nylund
Anders
A
Höglund
A Urban
AU
D000109:Acetylcholine / Q000378:metabolism*; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D007649:Ketamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D000778:Anesthetics, Dissociative; D018685:Anesthetics, Inhalation; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D007649:Ketamine; D008464:Mecamylamine; D007530:Isoflurane; C082748:epibatidine; D000109:Acetylcholine; C033419:norketamine