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Caden Hearn; Thesis.pdf (6.72 MB)

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EFFECTS OF FENTANYL AND D-CYSTEINE ETHYL ESTER ON CA2+ DYNAMICS IN HETEROGENOUS CELL CULTURES DERIVED FROM THE RAT HIPPOCAMPUS

Hearn, Caden
http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1684245455819422

Abstract Details

2023, BS, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
The opioid epidemic is a major health crisis in the U.S., resulting in an estimated 80,816 deaths in 2021. Overdose results in Opioid-Induced Respiratory Depression (OIRD) often treated by administration of competitive opioid receptor antagonists such as naloxone. However, these drugs are not effective against highly potent synthetic opioids (e.g., fentanyl) and are poorly suited for the prevention and/or treatment of opioid-craving or addiction. D-cysteine ethyl ester (D-CYSee) has been shown to prevent OIRD and disrupt the acquisition of fentanyl-induced seeking behaviors in rats. The Hippocampus (Hipp) has been established as a vital region for the encoding of drug-associated cues and contexts. Thus, the effects of D-CYSee and fentanyl on intrinsic calcium activity in heterogeneous cell cultures derived from the Hipp of P0 Sprague Dawley rat pups were observed. Males and females were cultured separately so sex differences in the cellular response to fentanyl and D-CYSee could be determined. Cells were cultured for 12-days, loaded with a fluorescent Ca2+ probe, Cal-520 AM, and imaged on an inverted microscope. It was found that fentanyl induced a transient Ca2+ peak in neurons derived from males but not females and in astrocytes derived from both sexes. Pretreatment with D-CYSee prevented this peak in neurons but only modulated it in astrocytes. This demonstrated not only a cellular basis for D-CYSee's ability to prevent drug seeking behavior, but also a clear sexual dimorphism in cellular responding to exogenous opioids within the hippocampus.
Derek Damron (Advisor)
Elda Hegmann (Committee Member)
Aleisha Moore (Committee Member)
Soumitra Basu (Committee Member)
75 p.
Biology; Cellular Biology; Neurosciences; Pharmacology
Calcium Imaging; Fentanyl; Opioid Use Disorder; Addiction

Recommended Citations

Citations

  • Hearn, C. (2023). EFFECTS OF FENTANYL AND D-CYSTEINE ETHYL ESTER ON CA2+ DYNAMICS IN HETEROGENOUS CELL CULTURES DERIVED FROM THE RAT HIPPOCAMPUS [Undergraduate thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1684245455819422

    APA Style (7th edition)

  • Hearn, Caden. EFFECTS OF FENTANYL AND D-CYSTEINE ETHYL ESTER ON CA2+ DYNAMICS IN HETEROGENOUS CELL CULTURES DERIVED FROM THE RAT HIPPOCAMPUS. 2023. Kent State University, Undergraduate thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1684245455819422.

    MLA Style (8th edition)

  • Hearn, Caden. "EFFECTS OF FENTANYL AND D-CYSTEINE ETHYL ESTER ON CA2+ DYNAMICS IN HETEROGENOUS CELL CULTURES DERIVED FROM THE RAT HIPPOCAMPUS." Undergraduate thesis, Kent State University, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1684245455819422

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Kent State University Honors College and OhioLINK.