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All Subjects: cognitive
Creators: Gallitano-Mendel, Amelia
Creators: Hooyman, Andrew

mGluR5 Positive allosteric modulation as a novel therapeutic target for the cognitive deficits associated with schizophrenia

Description

Patients with schizophrenia have impaired cognitive flexibility, as evidenced by behaviors of perseveration. Cognitive impairments may be due to dysregulation of glutamate and/or loss of neuronal plasticity in the medial prefrontal cortex (mPFC). The purpose of these studies was to examine the effects of mGluR5 positive allosteric modulators (PAMs) alone and in combination with the NMDAR antagonist MK-801, a pharmacological model of schizophrenia. An operant-based cognitive set-shifting task was utilized to assess cognitive flexibility, in vivo microdialysis procedures to measure extracellular glutamate levels in the mPFC, and diolistic labeling to assess the effects on dendritic spine density and morphology in the mPFC. Results revealed that chronic administration of the mGluR5 PAM CDPPB was able to significantly reduce the effects of chronically administered MK-801 on both behavioral perseveration and glutamate neurotransmission. Results also showed that CDPPB had no evidence of an effect on dendritic spine density or morphology, but the mGluR5 negative allosteric modulator fenobam caused significant increases in spine density and the frequency of occurrence of spines with smaller head diameters. Conclusions include that CDPPB is able to reverse MK-801 induced cognitive deficits as well as alterations in mPFC glutamate neurochemistry. The culmination of these studies add further support for targeting mGluR5 with PAMs as a novel mechanism to alleviate cognitive impairments in patients with schizophrenia.

ContributorsLaCrosse, Amber (Author) / Olive, Michael (Committee member) / Gallitano-Mendel, Amelia (Committee member) / Sanabria, Federico (Committee member) / Hammer, Ronald (Committee member) / Arizona State University (Publisher)

Created2014

Impacts of Age on Neuropsychological Task Performance

Description

The purpose of this study was to test the reproducibility of the current data set. It was hypothesized that older adults’ scores on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) would decrease from their initial visit to their one year follow-up visit and that greater overall age is associated with worse performance. Overall, the older adults with a follow-up visit in this study experienced greater decline on the RBANS DMI than on the RBANS total scaled score. There seems to be a negative trend in which individuals with higher first-visit VCI scores experience greater improvement on the first trial of the motor task with the non-dominant hand. The same trend can be seen in DMI scores where higher initial DMI scores are associated with greater improvement on the first non-dominant hand trial of the motor task. This initial trend suggests that visuospatial scores have an association with long-term change in the motor task. The number of participants in this data set were limited, thus more data will be needed to increase confidence in conclusions about these relationships in the future.

ContributorsDettmer, Alaina Nicole (Author) / Schaefer, Sydney (Thesis director) / Hooyman, Andrew (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)

Created2021-05