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CELLULAR AND BEHAVIORAL CHARACTARIZATION OF δ-OPIOID RECEPTOR MEDIATED ß-ARRESTIN SIGNALING
The following thesis will focus on understanding the downstream behavioral effects of δORmediated β-arrestinsignaling. δORagonists have been implicated as effective targets for a variety of diseases, however detrimental side effects of opioid-targeting agonists limit their clinical use. δORagonists specifically can induce seizures, however the underlying mechanism contributing to this behavior is unknown. We review this phenomenon in more detail, highlighting current agonists known to induce seizures and potential circuits and pathways involved. Our work suggests β-arrestinsignaling is involved, specifically β-arrestin2 mediated signaling may be largely contributing to δORagonist-induced seizure behavior. As it is possible the β-arrestinisoforms have unique roles in seizure behavior, we also analyzed methods in which to provoke β-arrestinisoform bias of δORtargeting compounds. Though the full mechanism relating δORagonists with seizures remains unknown, our work provides foundational detail of this behavior, implicating the importance of β-arrestinisoform signaling through δOR; allowing for future studies to full define this seizure pathway and develop δORsafer agonists.
- Doctor of Philosophy
- Medicinal Chemistry and Molecular Pharmacology
- West Lafayette