TY - JOUR

T1 - The effect of ketamine on intraspinal acetylcholine release

T2 - involvement of spinal nicotinic receptors

AU - Abelson, Klas S P

AU - Goldkuhl, Renée Röstlinger

AU - Nylund, Anders

AU - Höglund, A Urban

PY - 2006/3/18

Y1 - 2006/3/18

N2 - 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.

AB - 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.

KW - Acetylcholine

KW - Anesthetics, Dissociative

KW - Anesthetics, Inhalation

KW - Animals

KW - Bicyclo Compounds, Heterocyclic

KW - Isoflurane

KW - Ketamine

KW - Male

KW - Mecamylamine

KW - Nicotinic Agonists

KW - Nicotinic Antagonists

KW - Pyridines

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Nicotinic

KW - Spinal Cord

KW - Time Factors

M3 - Journal article

C2 - 16612840

VL - 534

SP - 122

EP - 128

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -