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Midbrain µ-Opioidergic Neural Circuits Facilitate Negative Affect in Morphine Withdrawal Adrienne Jo
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Jo, Adrienne, author.
- Language:
- English
- Subjects (All):
- Pharmacology.
- Neurosciences.
- Biomedical engineering.
- Behavioral psychology.
- Clinical psychology.
- 0419.
- 0317.
- 0541.
- 0622.
- 0384.
- Local Subjects:
- Pharmacology.
- Neurosciences.
- Biomedical engineering.
- Behavioral psychology.
- Clinical psychology.
- 0419.
- 0317.
- 0541.
- 0622.
- 0384.
- Physical Description:
- 1 electronic resource (135 pages)
- Contained In:
- Dissertations Abstracts International 86-07B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2024
- Language Note:
- English
- Summary:
- Opioid use disorder (OUD) is a chronic, relapsing condition driven by maladaptations in critical reward and aversion circuits that perpetuate drug-seeking behavior and exacerbate negative affective states upon cessation of opioid exposure. While mu-opioid receptors (MORs) in the ventral tegmental area (VTA) are central to opioid reinforcement, the remodeling of their structural connectivity during chronic morphine-seeking behavior and their role in negative affect during protracted withdrawal - the weeks to months following opioid cessation - remain unclear. This dissertation seeks to investigate the contribution of VTAMOR neurons to chronic morphineseeking behavior, acute withdrawal, and negative affective behaviors during protracted withdrawal. Using an oral morphine administration model, we observed that chronic morphine exposure increases lateral hypothalamus (LH) monosynaptic inputs to VTAMOR neurons and induces elevated social deficit-, anxiety-, and despair-related behaviors during a 4-week withdrawal period. VTAMOR neurons exhibit increased neuronal activation at the onset of withdrawal and are connected to prominent reward and aversion structures. Additionally, VTAMORs were identified as critical modulators of withdrawal-induced low sociability and neuronal activation in the anterior cingulate cortex (ACC) in response to an acute morphine challenge dose during protracted withdrawal. These findings underscore the critical role of VTAMOR neurons and their associated circuits in driving opioid-seeking behavior and low sociability during protracted withdrawal, positioning them as potential mechanistic targets for alleviating negative affective states during opioid withdrawal
- Notes:
- Source: Dissertations Abstracts International, Volume: 86-07, Section: B.
- Advisors: Blendy, Julie A.; Corder, Gregory F. Committee members: Heller, Elizabeth A.; Berrettini, Wade; Betley, Nicholas
- Ph.D. University of Pennsylvania 2024
- Local Notes:
- School code: 0175
- ISBN:
- 9798302183422
- Access Restriction:
- Restricted for use by site license
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