The effect of a GABA receptor agonist on sleep deficiency in a Fragile X syndrome mouse model
Thursday, September 14, 2017 — Poster Session III
- A Torossian
- RM Saré
- CB Smith
Fragile X syndrome (FXS) is a developmental disorder caused by genetic silencing of the fragile x mental retardation 1 (FMR1) gene. Those with FXS not only experience intellectual disability and exhibit autistic behaviors, but also physiological abnormalities including reduced sleep. Our studies of a mouse model of FXS, Fmr1 KO, demonstrate reduced sleep compared to controls. Sleep regulation, particularly sleep initiation, is associated with GABA receptor activation. Fmr1 KO mice exhibit decreased levels of GABAA and GABAB receptors, indicating that GABA pathways are affected in FXS. Our previous studies have shown that a GABAB receptor agonist, R-baclofen, reverses several behavioral phenotypes in FXS. In the present study, we test the effects of R-baclofen treatment on sleep. Adult male Fmr1 KO mice (C57BL/6J) (n=20) were singly housed and monitored for sleep duration in both light and dark cycles by means of non-invasive home-cage activity monitoring. Our preliminary data showed that sleep was improved during the light cycle with R-baclofen treatment. To improve experimental design, mice received daily i.p. injections for 11 days at the start of the light cycle (6AM) as follows: 5-day habituation period (saline injections), 3-day period (saline injections) with sleep monitoring, and 2-day period of R-baclofen (1.5mg/kg) treatment with sleep monitoring. Sleep was recorded continuously over the last 5 days. We compared sleep in the vehicle-injection period with the R-baclofen treatment period by means of paired t-tests. These data have the potential to highlight the benefits of R-baclofen as a possible multi-purpose treatment option for FXS.