Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome.
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.
Fernandez
Fabian
F
Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University, Palo Alto, California 94304-5485, USA.
Morishita
Wade
W
Zuniga
Elizabeth
E
Nguyen
James
J
Blank
Martina
M
Malenka
Robert C
RC
Garner
Craig C
CC
D000818:Animals; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications*; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology / Q000627:therapeutic use*
D018756:GABA Antagonists; D010433:Pentylenetetrazole; D010852:Picrotoxin