Extrasynaptic GABAA receptors in central medial thalamus mediate anesthesia in rats

Eur J Pharmacol. 2024 Jun 5:972:176561. doi: 10.1016/j.ejphar.2024.176561. Epub 2024 Apr 4.


Neuronal depression in the thalamus underlies anesthetic-induced loss of consciousness, while the precise sub-thalamus nuclei and molecular targets involved remain to be elucidated. The present study investigated the role of extrasynaptic GABAA receptors in the central medial thalamic nucleus (CM) in anesthesia induced by gaboxadol (THIP) and diazepam (DZP) in rats. Local lesion of the CM led to a decrease in the duration of loss of righting reflex induced by THIP and DZP. CM microinjection of THIP but not DZP induced anesthesia. The absence of righting reflex in THIP-treated rats was consistent with the increase of low frequency oscillations in the delta band in the medial prefrontal cortex. CM microinjection of GABAA receptor antagonist SR95531 significantly attenuated the anesthesia induced by systemically-administered THIP, but not DZP. Moreover, the rats with declined expression of GABAA receptor δ-subunit in the CM were less responsive to THIP or DZP. These findings explained a novel mechanism of THIP-induced loss of consciousness and highlighted the role of CM extrasynaptic GABAA receptors in mediating anesthesia.

Keywords: Central medial thalamic nucleus; Diazepam; Gaboxadol; Loss of righting reflex.

MeSH terms

  • Anesthesia*
  • Animals
  • Diazepam / pharmacology
  • Isoxazoles* / pharmacology
  • Male
  • Mediodorsal Thalamic Nucleus / drug effects
  • Mediodorsal Thalamic Nucleus / metabolism
  • Mediodorsal Thalamic Nucleus / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A* / metabolism
  • Reflex, Righting / drug effects
  • Synapses / drug effects
  • Synapses / metabolism
  • Thalamus / drug effects
  • Thalamus / metabolism


  • Receptors, GABA-A
  • Isoxazoles
  • gaboxadol
  • Diazepam