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.
Sou
J-H
JH
Institute of Pharmacology and Toxicology, Tzu Chi University Hualien, Taiwan, R.O.C.
Chan
M-H
MH
Chen
H-H
HH
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