Carbon dioxide inhalation, stress and anxiogenic drugs reduce the function of GABAA receptor complex in the rat brain

Prog Neuropsychopharmacol Biol Psychiatry. 1993 Jul;17(4):651-61. doi: 10.1016/0278-5846(93)90012-h.

Abstract

1. The effect of different stressful stimuli on the function of the GABAA-ionophore receptor complex was evaluated by measuring the binding of 35S-TBPS to the chloride channel associated recognition sites. 2. Foot-shock stress enhanced 35S-TBPS binding in membrane preparation from rat cerebral cortex. The effect of foot-shock on 35S-TBPS binding was mimicked by the anxiogenic and proconvulsant beta-carboline FG 7142 and antagonized by anxiolytic benzodiazepines and by the novel anxiolytic and anticonvulsant beta-carboline, abecarnil. 3. A brief exposure of rats to CO2 inhalation produced, like foot-shock and FG 7142, a marked increase of 35S-TBPS binding in the cerebral cortex, cerebellum and hippocampus. The effect of CO2 inhalation was maximal 10 min after treatment and return to control value in 2 hours. Previous administration of anxiolytic drugs (alprazolam and abecarnil) completely prevented the CO2 inhalation-induced increase of 35S-TBPS binding. 4. All together these data strongly suggest that carbon dioxide inhalation, like stress and anxiogenic drugs, decreases the function of the GABAA receptor complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Anxiety / chemically induced
  • Anxiety / metabolism*
  • Benzodiazepines
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology*
  • Bridged Bicyclo Compounds / metabolism
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Carbolines / pharmacology
  • Carbon Dioxide / administration & dosage
  • Carbon Dioxide / pharmacology*
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Chloride Channels
  • Electroshock
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Male
  • Membrane Proteins / drug effects
  • Membrane Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism*
  • Stress, Psychological / metabolism*

Substances

  • Anti-Anxiety Agents
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Carbolines
  • Chloride Channels
  • Ion Channels
  • Membrane Proteins
  • Receptors, GABA-A
  • Benzodiazepines
  • Carbon Dioxide
  • FG 7142
  • tert-butylbicyclophosphorothionate