TY  - JOUR
AU  - Colas, Damien
AU  - Chuluun, Bayarsaikhan
AU  - Garner, Craig C
AU  - Heller, H Craig
TI  - Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome.
JO  - Neurobiology of learning and memory
VL  - 140
SN  - 1074-7427
CY  - Orlando, Fla.
PB  - Academic Press
M1  - DZNE-2020-05503
SP  - 11-16
PY  - 2017
AB  - Down syndrome (DS) is a common genetic cause of intellectual disability yet no pro-cognitive drug therapies are approved for human use. Mechanistic studies in a mouse model of DS (Ts65Dn mice) demonstrate that impaired cognitive function is due to excessive neuronal inhibitory tone. These deficits are normalized by chronic, short-term low doses of GABAA receptor (GABAAR) antagonists in adult animals, but none of the compounds investigated are approved for human use. We explored the therapeutic potential of flumazenil (FLUM), a GABAAR antagonist working at the benzodiazepine binding site that has FDA approval. Long-term memory was assessed by the Novel Object Recognition (NOR) testing in Ts65Dn mice after acute or short-term chronic treatment with FLUM. Short-term, low, chronic dose regimens of FLUM elicit long-lasting (>1week) normalization of cognitive function in both young and aged mice. FLUM at low dosages produces long lasting cognitive improvements and has the potential of fulfilling an unmet therapeutic need in DS.
KW  - Animals
KW  - Cognition: drug effects
KW  - Disease Models, Animal
KW  - Down Syndrome: drug therapy
KW  - Down Syndrome: genetics
KW  - Flumazenil: pharmacology
KW  - Flumazenil: therapeutic use
KW  - GABA Modulators: pharmacology
KW  - GABA Modulators: therapeutic use
KW  - Male
KW  - Memory Disorders: drug therapy
KW  - Memory, Long-Term: drug effects
KW  - Mice
KW  - GABA Modulators (NLM Chemicals)
KW  - Flumazenil (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28215510
DO  - DOI:10.1016/j.nlm.2017.02.006
UR  - https://pub.dzne.de/record/139181
ER  -