Self-injurious behavior is a common problem among several neurodevelopmental and psychiatric disorders. There are currently few safe and reliable treatments for the behavior, in part because of our limited understanding of its neurobiological basis. Recently, we demonstrated that administration of the L-type calcium channel agonist Bay K 8644 can acutely provoke self-injury in weanling mice, providing a new animal model that can be exploited to study the neurobiology of this unusual behavior.
Specific Aim 1 addresses the neuroanatomical substrates for self-injurious behavior provoked by Bay K 8644 with two functional histochemical mapping methods, induction of the mRNA encoding the immediate-early gene c-fos and 2-deoxyglucose autoradiography. Our hypothesis for this aim is that Bay K 8644 causes self-injurious behavior by influencing the functions of the caudoputamen, the region most often implicated in the expression of self-injurious behavior in other studies.
Specific Aims 2 -3 address the neuropharmacological basis for self-injurious behavior provoked by Bay K 8644, and in particular the involvement of dopaminergic and serotonergic systems, the two neurotransmitter systems most often implicated as mediators of the behavior in prior studies. Our hypothesis for these aims is that Bay K 8644 causes self-injurious behavior by activating specific dopaminergic and serotonergic receptor subtypes.
Specific Aim 4 addresses the role of L-type calcium channels in another well-characterized model for self-injurious behavior, the administration of dopaminergic or serotonergic agonists to rats that had received 6-hydroxydopamine lesions during the neonatal period. We will test the ability of calcium channel antagonists to prevent the expression of self-injurious behavior in this model. Our hypothesis for this aim is that the L-type calcium channels may provide a """"""""final common pathway"""""""" for the expression of self-injury. These studies have direct relevance for understanding the neuroanatomical and neurochemical basis for self-injurious behavior and direct implications for a potential novel treatment strategy.
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