The GABA/benzodiazepine receptor chloride channel complex during repeated episodes of physical ethanol dependence in the rat.
The GABA/benzodiazepine (BZ) receptor chloride channel complex was investigated during repeated episodes of ethanol intoxication and withdrawal in the rat; the intragastric intoxication technique was applied and the severity of intoxication, withdrawal and number of seizures were recorded. The following groups were studied after decapitation during withdrawal 10-16 h after the last ethanol feeding: A) isocalorically fed controls not receiving ethanol; B) isocalorical controls subjected to a single ethanol intoxication period; C) animals subjected to 15 intoxication-withdrawal episodes (spontaneous seizures); D) same as C, but without developing seizures. A radio receptor technique was applied in the characterization of the receptor complex comprising specific binding to the BZ-receptor, the chloride channel and the GABA receptor by 3H-diazepam, 35S-TBPS and 3H-muscimol, respectively. The allosteric couplings among the components of the receptor complex were studied by 3H-diazepam and 35S-TBPS binding enhancement tests involving muscimol, ZK 93423 and DMCM. Cortex, hippocampus and cerebellum were the brain regions studied. Except for a reduced specific binding of 3H-diazepam in cerebellum, there were no indications of changes in specific binding to any part of the receptor complex. The allosteric coupling of BZ and GABA receptors as well as chloride channel-BZ receptors were unchanged in all groups. It is notable that no changes at all could be related to number of intoxication-withdrawal episodes or to the development of seizures. Thus, the present study gave no indication that the GABA/benzodiazepine receptor chloride channel complex is directly involved in the augmentation of cerebral nervous system excitability (seizures) during repeated episodes of physical ethanol dependence.
Ulrichsen
J
J
Department of Psychiatry, Rigshospitalet, Copenhagen, Denmark.
Clemmesen
L
L
Barry
D
D
Hemmingsen
R
R
D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D009118:Muscimol; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D013462:Sulfur Radioisotopes
D002712:Chlorides; D007473:Ion Channels; D011963:Receptors, GABA-A; D013462:Sulfur Radioisotopes; D009118:Muscimol; D003975:Diazepam