Impaired inhibition of epileptiform activity by baclofen, but not by adenosine in the weaver hippocampus
The weaver defect results in a loss of baclofen- and adenosine-gated K+ conductance in the hippocampus of adult homozygous (wv/wv) mice. In addition, suppression of hippocampal epileptiform activity by baclofen is impaired (Jarolimek, W., Bäurle, J., Misgeld, U., 1998. Pore mutation in a G protein-...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2000
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| In: |
Neuropharmacology
Year: 2000, Volume: 39, Issue: 2, Pages: 246-253 |
| ISSN: | 1873-7064 |
| DOI: | 10.1016/S0028-3908(99)00089-1 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/S0028-3908(99)00089-1 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0028390899000891 
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| Author Notes: | Wolfgang Jarolimek, Jörg Bäurle, Ulrich Misgeld |
| Summary: | The weaver defect results in a loss of baclofen- and adenosine-gated K+ conductance in the hippocampus of adult homozygous (wv/wv) mice. In addition, suppression of hippocampal epileptiform activity by baclofen is impaired (Jarolimek, W., Bäurle, J., Misgeld, U., 1998. Pore mutation in a G protein-gated inwardly rectifying K+ channel subunit causes loss of K+ dependent inhibition in weaver hippocampus. Journal of Neuroscience 18, 4001-4007). We used wv/wv and wild-type (+/+) mice to determine whether K+ conductance increases are essential for the suppression of epileptiform activity by R-baclofen and adenosine in disinhibited hippocampal slices. In wv/wv mice R-baclofen was less potent by two orders of magnitude in reducing the frequency of spontaneous synchronous burst discharges than in +/+ mice. Endogenous adenosine and adenosine A1 receptor agonists differed only slightly in their efficacy to inhibit spontaneous synchronous burst discharges in wv/wv and +/+ mice. The findings on adenosine A1 receptors suggest that the varied efficacy of R-baclofen in wv/wv and +/+ mice may not be explained solely on the basis of a loss of ligand-gated K+ conductance. Therefore, we investigated the affinity of GABAB receptors for the antagonist CGP55845A in wv/wv and +/+ hippocampi. Schild plot analysis revealed a KD for the GABAB antagonist CGP55845A 10 fold higher in wv/wv than in +/+ mice. The data suggest that an alteration of GABAB receptors could contribute to the reduced efficacy of R-baclofen to suppress hippocampal epileptiform activity in weaver mice, while the suppression by adenosine remains largely unaffected. |
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| Item Description: | Online 27 December 1999 Gesehen am 27.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1873-7064 |
| DOI: | 10.1016/S0028-3908(99)00089-1 |