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GABA B Receptor‐Mediated Effects in Synaptosomes of Lethargic ( lh/lh ) Mice
Author(s) -
Lin Fuhsiung,
Wang Ying,
Lin Susie,
Cao Zhen,
Hosford David A.
Publication year - 1995
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 - 10.1046/j.1471-4159.1995.65052087.x
Subject(s) - neocortex , gabab receptor , medicine , endocrinology , receptor , baclofen , thalamus , gabaa receptor , chemistry , biology , neuroscience , agonist
Previously, we have shown a significant increase in number of GABA B receptor binding sites in neocortex and thalamus of lethargic ( lh/lh ) mice, a mutant strain exhibiting absence seizures. This study was performed to test our hypothesis that presynaptic GABA B receptors would inhibit [ 3 H]GABA release to a greater degree in lh/lh mice compared with their nonepileptic littermates (designated +/+). Synaptosomes isolated from neocortex and thalamus of age‐matched male lh/lh and +/+ mice were similar in uptake of [ 3 H]GABA. In the neocortical preparation, baclofen dose‐dependently inhibited [ 3 H]GABA release evoked by 12 m M KCl, an effect mediated by GABA B receptors. The maximal inhibition ( I max ) value was significantly greater (80%) in lh/lh than +/+ mice, whereas the IC 50 (3 µ M ) was unchanged. In the thalamic preparation, the effect of baclofen (50 µ M ) was 58% less robust in lh/lh mice. Other effects mediated by GABA B receptors (inhibitions in Ca 2+ uptake and cyclic AMP formation) were also significantly reduced in thalamic synaptosomes from lh/lh mice. These data suggest a greater presynaptic GABA B receptor‐mediated effect in neocortex and a reduced effect in thalamic nuclei of lh/lh mice. It is possible that selective effects of presynaptic GABA B receptors on GABA release in neocortex and thalamic nuclei of lh/lh mice may contribute to mechanisms underlying absence seizures.