Premium
Decrease in the Function of the γ‐Aminobutyric Acid‐Coupled Chloride Channel Produced by the Repeated Administration of Pentylenetetrazol to Rats
Author(s) -
Corda M. G.,
Giorgi O.,
Longoni B.,
Orlandi M.,
Biggio G.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb03127.x
Subject(s) - pentylenetetrazol , kindling , pharmacology , chemistry , sensitization , cerebral cortex , anesthesia , stimulation , medicine , epilepsy , anticonvulsant , immunology , psychiatry
Abstract: The acute administration of pentylenetetrazol (PTZ; 25–75 mg/kg i.p.) failed to modify the specific binding of t ‐[ 35 S]butylbicyclophosphorothionate ([ 35 S]TBPS) to membrane preparations from the cerebral cortex of the rat. In contrast, the repeated administration of PTZ (30 mg/kg i.p., three times a week for 12 weeks) reduced by 26% the density of [ 33 S]TBPS binding sites without modifying the dissociation constant. This effect was observed 3 days after the last PTZ administration. A parallel reduction of 7‐amino‐butyric acid (GABA)‐stimulated 36 CI − uptake was measured in the cerebral cortex of PTZ‐treated rats 3 days after the last injection. The repeated administration of PTZ produced sensitization to the drug, or chemical kindling. In fact, no convulsions were observed in the first week of treatment, but all the animals became sensitized to PTZ by the 12th week. The results are consistent with the hypothesis that chronic treatment with PTZ at a subconvulsant dose causes a decrease in GABA‐coupled chloride channel activity that may be related to the chemical kindling produced by this compound.