Carbon dioxide inhalation, stress and anxiogenic drugs reduce the function of GABAA receptor complex in the rat brain.
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.
Concas
A
A
Department of Experimental Biology, University of Cagliari, Italy.
Sanna
E
E
Cuccheddu
T
T
Mascia
M P
MP
Santoro
G
G
Maciocco
E
E
Biggio
G
G
D000280:Administration, Inhalation; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D001569:Benzodiazepines; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002243:Carbolines / Q000494:pharmacology; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018118:Chloride Channels; D004597:Electroshock; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002243:Carbolines; D018118:Chloride Channels; D007473:Ion Channels; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D002245:Carbon Dioxide; C035874:FG 7142; C037476:tert-butylbicyclophosphorothionate