Ketamine, but not propofol, anaesthesia is regulated by metabotropic glutamate 5 receptors.
BACKGROUND
Group I metabotropic glutamate receptors (mGluRs) have been reported to regulate N-methyl-d-aspartate (NMDA) receptor function in various brain regions. The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) can potentiate NMDA antagonists such as PCP and MK-801-induced behavioural responses. In the present study, the role of group I mGluRs on ketamine- and propofol-induced general anaesthesia was examined.


METHODS
Mice were pretreated with various doses of the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG), selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) and mGluR5 antagonist MPEP followed by administration of ketamine (120 mg kg(-1)) or propofol (140 mg kg(-1)) to induce anaesthesia. The duration of loss of righting reflex was recorded.


RESULTS
DHPG and CHPG antagonized and MPEP potentiated ketamine-induced anaesthesia in a dose-dependent manner. CPCCOEt was ineffective. However, propofol-induced anaesthesia was not affected after manipulating mGluR1 and mGluR5 receptors.


CONCLUSIONS
mGluR5 receptors play an important role in modulation of anaesthesia induced by ketamine, but not propofol.
Institute of Pharmacology and Toxicology, Tzu Chi University Hualien, Taiwan, R.O.C.
J-H
JH
Sou
M-H
MH
Chan
H-H
HH
Chen
D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007649:Ketamine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D010648:Phenylacetates / Q000494:pharmacology; D015742:Propofol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012018:Reflex / Q000187:drug effects
C107349:2-chloro-5-hydroxyphenylglycine; C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D002867:Chromones; C578936:Grm5 protein, mouse; D010648:Phenylacetates; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D008734:Methoxyhydroxyphenylglycol; D007649:Ketamine; C121465:6-methyl-2-(phenylethynyl)pyridine; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol; D015742:Propofol