Book Description

ABSTRACT: Self-injury is a debilitating feature of neurodevelopmental disorders, including autism-spectrum disorders and genetic disorders like Lesch-Nyhan, Prader-Willi, Rett, and Fragile X syndromes. Self-injury is a devastating disorder that involves not only bodily injury (even as severe as broken bones and amputation of tongues, lips, and fingers) but also leads to exclusion of the self-injurer from social activities and cognitive therapies and causes severe distress for family and caretakers. As such, reducing selfinjury in these populations would positively impact overall health, socialization, cognitive function, and relationships with family, friends, and caregivers. Furthermore, understanding the neurobiological basis of this behavior disorder will help to elucidate genetic variables that predispose vulnerability and gene-environment interactions that promote the development of self-injurious patterns of behavior. To elucidate neurobiological changes associated with the induction and expression of self-injurious behavior, an analysis of several brain regions and circuits was conducted using a rat model of self-injury. In this model, pemoline, an indirect monoamine agonist, is administered repeatedly across days, which causes the development of repetitive behavior and self-biting in rats. Repeated stress exposure increased the severity of pemoline-induced self-injury, suggesting that the biochemical stress response may cross-sensitize with the stimulant properties of pemoline to potentiate self-injury. Relatedly, endogenous stress responsiveness correlated with the vulnerability to develop pemoline-induced self-injury. Pain thresholds of pemolinetreated rats were also evaluated and were found to be significantly greater than the pain thresholds of vehicle-treated rats.