Theses and Dissertations
Permanent URI for this collectionhttps://hdl.handle.net/10657.1/271
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Browsing Theses and Dissertations by Subject "5-HT2A receptor"
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Item An experimental therapy for opioid withdrawal syndrome(2023-12-04) Reed, Yvonne; Malin, David H.; Moreno, GeorginaThe ongoing opioid crisis in the United States needs alternative therapeutics. To explore the role of the 5-HT2A serotonin receptor in opioid physical dependence and withdrawal syndrome, morphine dependent rats were treated with pimavanserin, a highly selective 5-HT2A inverse agonist in current medical use. In experiment 1, rats were rendered morphine-dependent after seven days of continuous infusion at 0.6 mg/kg/hr. On the seventh day, morphine infusion ceased, and a day later, rats were injected with either 0.3 or 1.0 mg/kg pimavanserin or saline. A non-morphine dependent saline-infused control group received only saline. One hour post injection, rats were observed under blind conditions for somatically expressed behavioral withdrawal signs utilizing a validated observation checklist. Compared to morphine dependent/saline-injected rats, the non-dependent rats and both morphine-dependent pimavanserin dose groups exhibited significantly reduced withdrawal signs, p < .001, based on Tukey’s HSD test for non-independent pairwise comparisons. The higher pimavanserin dose (1.0 mg/kg) fully reversed the effect of morphine infusion on withdrawal signs, while the lower dose (0.3 mg/kg) largely reversed it. In experiment 2, utilizing only non-dependent/salineinfused rats, pimavanserin showed no significant effect on overall withdrawal signs. Given pimavanserin’s high selectivity for the 5-HT2A serotonin receptor, these findings indicate that the activity of this receptor plays a role in opioid physical dependence. These results suggest the need for further research on pimavanserin as a novel therapeutic for managing the aversive withdrawal symptoms associated with opioid withdrawal syndrome.Item The dose dependent effects of Pimavanserin on a modified rodent model of post-traumatic stress disorder(2020-12-07) Suzaki, Aoi; Malin, David H; Ward, Chstopher PPost-traumatic stress disorder (PTSD) is a persistent psychiatric disorder where patients develop symptoms from directly experiencing or witnessing traumatic events. The animal models are often used as preclinical studies for PTSD. Our research group previously found that the developed animal model of PTSD, which was composed of chronic and acute stress, successfully induced PTSD-like anxiety behaviors in the three behavioral measurements: elevated-plus maze, open field, and acoustic startle response. Additionally, the inverse antagonist drug Pimavanserin significantly reduced these fear-related behaviors in the animal model. In the current research, we examined the effects of each stressor, specifically the effect of social isolation, in addition to the replication of the effects of Pimavanserin on the animal model of PTSD, including the dose dependence of Pimavanserin. As a result, higher dose injections significantly reduced rats’ anxiety-level in the behavioral measures, while the smaller and no Pimavanserin injections did not change animals’ behaviors. In relation to the effect of social isolation, there was no significant difference between animals in the single housed group and pair housed group. These results strongly supported the role of 5-HT2A in our PTSD-animal model. Furthermore, from the results, it is highly expected that the 5-HT2A receptors’ inverse antagonists have positive therapeutic effects on PTSD patients.