Self-Injurious Behavior: An Animal Model of an Autism Endophenotype
Final rept. 15 May 2010-14 Dec 2011
FLORIDA UNIV GAINESVILLE
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Self-injurious behavior SIB is a debilitating characteristic that is prevalent in autism spectrum disorders ASD. Although the prevalence suggests that these children are highly vulnerable, the neurological mechanisms that confer vulnerability are unexplored. We have used an animal model to examine the expression and phosphorylation of DARPP-32, a signaling molecule that integrates dopaminergic and glutamatergic signaling, since these neurotransmitter systems are thought to play an important role in the etiology of SIB. In our model, SIB is brought about by repeated administration of the psychostimulant pemoline. We titrated the dose to a level that provokes robust SIB in about 50 of the rats, and identified an innate characteristic that confers vulnerability. When we pre-screened outbred Long-Evans rats for behavioral responsiveness to mild stress, the rats that were hyper-responsive HR self-injured more severely than less stress-responsive LR rats did. This finding has important implications for emotional and neurochemical factors that may contribute to vulnerability for SIB in ASD, and suggest that these children should be tested for stress-related vulnerability to develop SIB. In addition, we investigated DARPP-32 expression and activation phosphorylation in pemoline-treated HR and LR rats. The HR rats exhibited the most self-injury, and they had the highest levels of DARPP-32 expression. However, the pemoline-treatment did not differentially alter expression or phosphorylation of DARPP-32 in the HR vs. the LR rats. These findings suggest that a higher innate level of DARPP-32 in striatal medium spiny neurons may enhance vulnerability for pemoline-induced SIB, but the pemoline treatment does not induce self-injury through alterations in specific DARPP-32-mediated signaling mechanisms.
- Medicine and Medical Research