Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Neuroscience

Supervisor

Dr.Susanne Schmid

Abstract

Prepulse inhibition (PPI) of the acoustic startle response is a preattentive process disrupted in schizophrenia. NMDAR-antagonist induced PPI disruption has become a prevalent pharmacological model, however knowledge of the mechanism underlying NMDAR-antagonist induced PPI deficits (NAlPdef) remains incomplete. This work aims to examine the roles of NMDAR subtypes in the medial prefrontal cortex (mPFC) and the caudal pontine reticular nucleus (PnC) in NAlPdef in rats, and the effects of NMDAR antagonists on PPI and startle reactivity over the diurnal cycle. Results indicate that neither the PnC nor the diurnal cycle play a role in the mechanism underlying NAlPdef. However, microinjections of the NMDAR antagonist MK-801 to the mPFC caused significant disruption of PPI, while microinfusion of the NR2B-specific NMDAR antagonist ifenprodil to the mPFC caused trend level disruption of PPI. This work shows for the first time that NMDARs in the mPFC play a role in the mechanism underlying NAlPdef.

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