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The Oxytocin System's Contributions to the Negative Symptom Domain of Schizophrenia

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2022, MS, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Schizophrenia is a debilitating multi-etiological neurodevelopmental disorder with neural underpinnings that are most often linked to dysregulations in the dopaminergic and glutamatergic systems. However, there is also evidence that the oxytocin (Oxt) system may contribute to some of the negative symptoms, such as impaired social interactions and social motivation. Here, we wanted to explore how the presence or absence of oxytocin receptor signaling would affect behaviors in a phencyclidine (PCP)-withdrawal mouse model of schizophrenia. We hypothesized that mice lacking functional Oxt receptors (Oxtr) would have impaired social motivation and social approach behaviors following withdrawal from subchronic PCP treatment up and above that observed in control mice. To test this hypothesis, adult male Oxt wildtype (+/+), Oxt knockout (–/–), Oxtr wildtype (+/+), and Oxtr knockout (–/–) mice, generated from heterozygous breeding pairs, were administered subchronic PCP (5mg/kg) intraperitoneally, twice daily for seven days. Control animals were injected with an equivalent volume of saline on the same schedule. Following the week of injections, experimental animals were given another seven days to withdrawal; this has been shown to induce schizophrenia-like symptoms. In Experiment 1, on the first day following withdrawal, mice underwent a training protocol to learn how to complete a novel social motivation task. In Experiment 2, adult male Oxtr +/+ and Oxtr –/– mice were tested for locomotor activity in an open field test, sociability using a 3-chamber social interaction test, and depressive-like behaviors using a forced swim test across three consecutive days. Following the forced swim test, brain tissue was collected, sliced, and immunostained for expression of the c-fos immediate early gene. When analyzed, the data did not support our hypothesis as we found no genotypic-dependent effects of PCP on any of the behaviors measured. However, as would be expected, PCP-injected mice spent less time in the social chamber than their saline injected counterparts. Additionally, in the medial amygdala, expression of c-fos was elevated in Oxtr –/– mice relative to Oxtr +/+ controls. These data suggest that the social withdrawal induced in this schizophrenia model is not Oxtr-dependent.
Heather Caldwell (Advisor)
Devin Mueller (Committee Member)
John Johnson (Committee Member)
56 p.

Recommended Citations

Citations

  • Sapp, C. (2022). The Oxytocin System's Contributions to the Negative Symptom Domain of Schizophrenia [Master's thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1669466986826954

    APA Style (7th edition)

  • Sapp, Coleman. The Oxytocin System's Contributions to the Negative Symptom Domain of Schizophrenia. 2022. Kent State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1669466986826954.

    MLA Style (8th edition)

  • Sapp, Coleman. "The Oxytocin System's Contributions to the Negative Symptom Domain of Schizophrenia." Master's thesis, Kent State University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=kent1669466986826954

    Chicago Manual of Style (17th edition)