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Preclinical Investigations of Genetic Correlates of Alcohol Use Disorder = Investigaciones pre-clinicas de factores geneticos del desorden de uso de alcohol / Natalia Amaris Quijano Carde.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Quijano Carde, Natalia Amaris, author.
- Language:
- English
- Subjects (All):
- Pharmacology.
- Neurosciences.
- Pharmacology--Penn dissertations.
- Penn dissertations--Pharmacology.
- Local Subjects:
- Pharmacology.
- Neurosciences.
- Pharmacology--Penn dissertations.
- Penn dissertations--Pharmacology.
- Physical Description:
- 1 online resource (239 pages)
- Distribution:
- Ann Arbor : ProQuest Dissertations & Theses, 2022
- Contained In:
- Dissertations Abstracts International 84-02B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.
- Language Note:
- English
- Summary:
- Alcohol use disorder (AUD) is a common neuropsychiatric condition characterized by uncontrolled alcohol use that has serious medical and social consequences. AUD is heritable and intense work has been done to characterize its genetic basis. Preclinical studies have been critical in describing the functional significance of genes associated with AUD and have advanced our understanding of the neurobiological underpinnings of this disorder. This dissertation presents a collection of mouse studies that describe behavioral and neurochemical consequences of genetic or pharmacological manipulations of three systems genetically implicated in AUD: (i) the ZIP8 transporter, (ii) the GluK1-containing kainate receptors, and (iii) the α5-containing nicotinic acetylcholine receptors (nAChR). First, we describe disturbances in baseline behavior and increased volitional alcohol intake in animals lacking the ZIP8 transporter. We then report the effects of selective inhibition of GluK1-containing kainate receptors using LY466195 on ethanol consumption, reinforcement, and withdrawal. In the third study, we describe how disruption of α5-containing nAChR function influences adolescent ethanol and nicotine consumption, as well as adult drug intake in a sex-specific manner. Finally, we propose a framework to investigate the spontaneous manifestation of ethanol withdrawal in mice voluntarily drinking alcohol in a model with high face validity. Altogether, this body of work contributes to the current understanding of the etiology of AUD.
- Notes:
- Source: Dissertations Abstracts International, Volume: 84-02, Section: B.
- Advisors: Bhatnagar, Seema; Committee members: Kranzler, Henry R.; Berrettini, Wade H.; Ramchandani, Vijay A.
- Department: Pharmacology.
- Ph.D. University of Pennsylvania 2022.
- Local Notes:
- School code: 0175
- ISBN:
- 9798837502293
- Access Restriction:
- Restricted for use by site license.
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