Ketamine, but not propofol, anaesthesia is regulated by metabotropic glutamate 5 receptors

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Abstract

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.

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