An experimental therapy for opioid withdrawal syndrome

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dc.contributor.committeeMemberMalin, David H.
dc.contributor.committeeMemberMoreno, Georgina
dc.creatorReed, Yvonne
dc.creator.orcid0009-0000-6547-1565
dc.date.accessioned2024-03-25T16:37:01Z
dc.date.available2024-03-25T16:37:01Z
dc.date.created2023-12
dc.date.issued2023-12-04
dc.date.submittedDecember 2023
dc.date.updated2024-03-25T16:37:02Z
dc.description.abstractThe 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.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10657.1/4932
dc.language.isoen
dc.subject5-HT2A receptor
dc.subjectopiate dependence
dc.subjectopioid withdrawal
dc.subjectmorphine dependence
dc.subjectmorphine withdrawal
dc.subjectpimavanserin
dc.subject5-HT2A inverse agonist
dc.subjectrat
dc.titleAn experimental therapy for opioid withdrawal syndrome
dc.typeThesis
dc.type.materialtext
thesis.degree.grantorUniversity of Houston-Clear Lake
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

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