Schizophrenia is one of the most prevalent neuropsychiatric disorders in our country today. By establishing the neural substrates mediating specific deficits of this disorder the development of better treatments might be accomplished. PPI (a measure of sensorimotor gating) is a normal cross-species occurrence that is deficient in schizophrenic patients. This impairment in PPI has been successfully modelled in rats through the use of DA agonists and these deficits have been then reversed using DA antagonists and antipsychotics. The goal of this project is to use recently developed """"""""knockout"""""""" mice to investigate the role of DA in the modulation of PPI. Background pharmacology studies will be conducted, as few experiments have been done using mice.
The second aim of this proposal is to characterize the D2 receptor knockout and the DAT knockout mice in PPI and locomotor activity sessions and investigate pharmacological manipulations of their behavior. In summary, this proposal seeks to determine the role of DA in the modulation of PPI and locomotor activity through the use of genetically altered mice.
| Ralph, R J; Varty, G B; Kelly, M A et al. (1999) The dopamine D2, but not D3 or D4, receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice. J Neurosci 19:4627-33 |
