DESCRIPTION (provided by applicant): A subset of motoric symptoms associated with autism includes mild, stereotypic to intense, self-injurious behaviors. In the past, these behaviors have been linked to dysfunction of brain dopamine but, unfortunately, clinical trials with dopamine antagonists have met with poor results. The accepted rodent model of self-injurious behavior relies on neonatal dopamine lesions followed by L-dopa administration to the adult. This model works well in rats but not in mice. In a series of studies using in situ hybridization as well as knockout and transgenic mice to explore the development of the topographic projections of brain dopaminergic neurons, it was observed that brain serotinergic systems are activated following neonatal damage to dopaminergic neurons. That is, it appeared that early dopamine lesions activated brain serotinergic systems. This observation was then linked to the induction of stereotypic and self-injurious behaviors in adult mice treated with high doses of amphetamine, doses which induced the release of both dopamine and serotonin. On the basis of these and other observations, a new animal model of self-injurious behaviors centering on the dual activation of brain dopamine and serotonin is proposed. In addition, based on this new model, the possible beneficial effects of risperidone, an antagonist of these transmitter systems, will be explored.
|Effective start/end date||9/30/01 → 8/31/05|
- National Institutes of Health: $73,700.00
- National Institutes of Health: $73,817.00
- National Institutes of Health: $72,267.00