Leen is a bio major and member of the Honors College and UMBC Women's Soccer team. Her father came to support her at URCAD. She wins a $50 gift certificate to the UMBC Bookstore! She presented her poster:
Title: β-arrestin2 Signaling Modulates Kappa Opioid Receptor Induced Sedation
Presenter: Leen Jawhar
Mentors: Laurie Sutton, Biological Sciences; Alyson Blount, Biological Sciences UMBC pHD student
Kappa opioid receptors (KORs) play an important role in regulating pain, itch, mood, and arousal, but the receptor’s clinical use is limited by adverse effects such as sedation and motor impairment. Although KOR activation produces sedative behaviors, the intracellular signaling mechanisms responsible for these effects remain poorly defined. KORs signal through two primary intracellular pathways: G protein and β-arrestin2 signaling. These pathways are canonically believed to mediate different behaviors however more research is coming out showing they aren’t as independent as initially thought. The central goal was to determine the specific contribution of β-arrestin2 signaling to KOR-induced sedation in vivo. To address this, we used conditional β-arrestin2 knockout mice where β-arrestin2 is removed from KOR-expressing neurons. A rotarod assay assessed sedation and motor coordination. Mice were treated with U50,488, a KOR agonist that activates both G protein and β-arrestin2 pathways, or Nalfurafine, a G protein-biased agonist with minimal β-arrestin2 recruitment. U50,488 induced sedation in wild-type, whereas β-arrestin2 knockout mice showed reduced sedation. Nalfurine produced motor impairment in WT mice which was reduced in β-arrestin2 knockouts. These findings demonstrate that β-arrestin2 recruitment is required for KOR-mediated sedation, providing insight into therapeutics development that have analgesic effects while minimizing sedative side effects.
Save the date for URCAD 31:
April 28, 2027
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