Presentation Abstract

Program#/Poster#: 245.17/U14
Presentation Title: Enhancement of α2,3-GABAA receptor signaling rescues autistic-like behaviors in a mouse model of autism
Location: Halls B-H
Presentation time: Sunday, Nov 10, 2013, 1:00 PM - 2:00 PM
Topic: ++C.07.c. Autism: Physiology and systems
Authors: *S. HAN, C. TAI, C. J. JONES, T. SCHEUER, W. A. CATTERALL;
Pharmacol., Univ. of Washington, Seattle, WA
Abstract: Autism spectrum disorder (ASD) may arise from increased ratio of excitatory to inhibitory neurotransmission in the brain. Many pharmacological treatments have been tested in ASD, but only limited success has been achieved. Here we report that BTBR T+tf/J (BTBR) mice, a well-established model of idiopathic autism, have reduced spontaneous GABAergic neurotransmission. Treatment with non-sedating/non-anxiolytic doses of benzodiazepines, which increase inhibitory neurotransmission through positive allosteric modulation of postsynaptic GABAA receptors, completely rescued autistic-like behaviors. Moreover, negative allosteric modulation of GABAA receptors induced autistic-like behaviors in otherwise normal C57BL/6J mice, suggesting a causal role for impaired inhibitory neurotransmission in autistic-like behaviors. The dramatic behavioral improvement after low-dose benzodiazepine treatment was subunit-specific; the α2,3-subunit-selective positive allosteric modulator L-838,417 was effective, but the α1-subunit-selective drug zolpidem exacerbated the social deficits. We propose that impaired GABAergic neurotransmission may contribute to ASD and that α2,3-subunit-selective positive GABAA receptor modulation may be an effective treatment.
Disclosures:  S. Han: None. C. Tai: None. C.J. Jones: None. T. Scheuer: None. W.A. Catterall: None.
Keyword(s): AUTISM
GABA
BENZODIAZEPINE
Support: NIH Grant R01 NS25704
Simons Foundation




Note: When adding items to your Itinerary, please click "Add Checked Selections to My Itinerary" on EACH page of your search results.

At the Meeting

Sessions/Events

Registration

Hotel/Travel

Exhibits

Abstracts

Fellowships, Awards, and Prizes

Frequently Asked Questions

Final Program

CME

Download Abstracts and
Daily Books to Your E-Reader Devices