Attentional Dysfunction in Schizophrenia: The Effects of Dual Orexin Receptor Blockade on an NMDA Receptor Hypofunction Model
Date Thesis Awarded
Honors Thesis -- Open Access
Bachelors of Science (BS)
Hypofunctionality at the N-Methyl-D-aspartic acid receptor (NMDAR) is a commonly used model of the neurodevelopmental disorder schizophrenia due to the complex circuitry changes that follow NMDAR blockade. While these animal models are very popular for modeling the cognitive deficits seen in schizophrenia, actual treatments for this disorder remain sparse. Orexins (hypocretins) are neuropeptides that are capable of modulating activity along pathways relevant to attention, but are rarely tested for their efficacy in attenuating attentional dysfunction. This study was conducted to determine if systemic administration of the dual orexin receptor antagonist filorexant (MK-6096) was able to attenuate sustained attentional dysfunction induced by administration of the NMDAR antagonist dizocilpine (MK-801). Results from this study demonstrate that administration of dizocilpine worsened task performance through an increase in response omissions; however, systemic administration of filorexant was not able to significantly attenuate attentional dysfunction. Future research should continue to investigate the orexinergic system as a potential modulator of the complex symptomatology present in attentional dysfunction associated with schizophrenia.
Little, Paige, "Attentional Dysfunction in Schizophrenia: The Effects of Dual Orexin Receptor Blockade on an NMDA Receptor Hypofunction Model" (2021). Undergraduate Honors Theses. William & Mary. Paper 1654.
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