Abstract
Withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) lines of mice have been genetically selected based on the severity of handling-induced convulsions after identical chronic ethanol exposure. The present experiments showed that naive WSP mice were more sensitive than WSR mice to a subconvulsant dose of picrotoxin, bicuculline or pentylenetetrazole as measured by the ability of these drugs to exacerbate handling-induced convulsions. This may reflect a difference between lines in the GABA-chloride channel. The density and affinity of [35S]t-butylbicyclophosphorothionate (TBPS) binding sites, a cage convulsant which binds to the picrotoxin site on the GABA-chloride channel, was measured in the frontal cortex, remainder of the cortex, cerebellum and hippocampus. The binding properties of [3H]flunitrazepam and the potency of γ-aminobutyric acid (GABA) to enhance flunitrazepam binding was characterized in whole brain samples. There were no differences between lines. The behavioral results suggest a role for the GABA-chloride channel in the differential ethanol withdrawal seizure behavior of WSR and WSP mice, but this is not due to changes in receptor densities or affinities.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 147-154 |
| Number of pages | 8 |
| Journal | European Journal of Pharmacology |
| Volume | 157 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Nov 22 1988 |
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Keywords
- Bicuculline
- Convulsions (handling-induced)
- Pentylenetetrazole
- Picrotoxin
- Withdrawal seizure-prone and withdrawal seizure-resistant lines, Selected lines, Pharmacogenetics
- [S]TBPS
- [H]Flunitrazepam
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
Differences in GABA activity between ethanol withdrawal seizure prone and resistant mice. / Feller, Daniel J.; Harris, R. Adron; Crabbe, John Jr.
In: European Journal of Pharmacology, Vol. 157, No. 2-3, 22.11.1988, p. 147-154.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differences in GABA activity between ethanol withdrawal seizure prone and resistant mice
AU - Feller, Daniel J.
AU - Harris, R. Adron
AU - Crabbe, John Jr
PY - 1988/11/22
Y1 - 1988/11/22
N2 - Withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) lines of mice have been genetically selected based on the severity of handling-induced convulsions after identical chronic ethanol exposure. The present experiments showed that naive WSP mice were more sensitive than WSR mice to a subconvulsant dose of picrotoxin, bicuculline or pentylenetetrazole as measured by the ability of these drugs to exacerbate handling-induced convulsions. This may reflect a difference between lines in the GABA-chloride channel. The density and affinity of [35S]t-butylbicyclophosphorothionate (TBPS) binding sites, a cage convulsant which binds to the picrotoxin site on the GABA-chloride channel, was measured in the frontal cortex, remainder of the cortex, cerebellum and hippocampus. The binding properties of [3H]flunitrazepam and the potency of γ-aminobutyric acid (GABA) to enhance flunitrazepam binding was characterized in whole brain samples. There were no differences between lines. The behavioral results suggest a role for the GABA-chloride channel in the differential ethanol withdrawal seizure behavior of WSR and WSP mice, but this is not due to changes in receptor densities or affinities.
AB - Withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) lines of mice have been genetically selected based on the severity of handling-induced convulsions after identical chronic ethanol exposure. The present experiments showed that naive WSP mice were more sensitive than WSR mice to a subconvulsant dose of picrotoxin, bicuculline or pentylenetetrazole as measured by the ability of these drugs to exacerbate handling-induced convulsions. This may reflect a difference between lines in the GABA-chloride channel. The density and affinity of [35S]t-butylbicyclophosphorothionate (TBPS) binding sites, a cage convulsant which binds to the picrotoxin site on the GABA-chloride channel, was measured in the frontal cortex, remainder of the cortex, cerebellum and hippocampus. The binding properties of [3H]flunitrazepam and the potency of γ-aminobutyric acid (GABA) to enhance flunitrazepam binding was characterized in whole brain samples. There were no differences between lines. The behavioral results suggest a role for the GABA-chloride channel in the differential ethanol withdrawal seizure behavior of WSR and WSP mice, but this is not due to changes in receptor densities or affinities.
KW - Bicuculline
KW - Convulsions (handling-induced)
KW - Pentylenetetrazole
KW - Picrotoxin
KW - Withdrawal seizure-prone and withdrawal seizure-resistant lines, Selected lines, Pharmacogenetics
KW - [S]TBPS
KW - [H]Flunitrazepam
UR - http://www.scopus.com/inward/record.url?scp=0023717329&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023717329&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(88)90377-9
DO - 10.1016/0014-2999(88)90377-9
M3 - Article
VL - 157
SP - 147
EP - 154
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2-3
ER -