Abstract
Ts65Dn mice, a model for Down syndrome, have excessive inhibition in the dentate gyrus, a condition that could compromise synaptic plasticity and mnemonic processing. We show that chronic systemic treatment of these mice with GABAA antagonists at non-epileptic doses causes a persistent post-drug recovery of cognition and long-term potentiation. These results suggest that over-inhibition contributes to intellectual disabilities associated with Down syndrome and that GABAA antagonists may be useful therapeutic agents for this disorder.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Behavior, Animal
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Cognition Disorders / drug therapy*
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Cognition Disorders / etiology*
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Disease Models, Animal
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Down Syndrome / complications*
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Electric Stimulation / methods
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / radiation effects
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Exploratory Behavior / physiology
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Female
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GABA Antagonists / pharmacology
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GABA Antagonists / therapeutic use*
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Hippocampus / cytology
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In Vitro Techniques
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Motor Activity / physiology
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Neurons / drug effects
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Neurons / physiology
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Neurons / radiation effects
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Pentylenetetrazole / pharmacology
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Picrotoxin / pharmacology
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Picrotoxin / therapeutic use*
Substances
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GABA Antagonists
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Picrotoxin
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Pentylenetetrazole