Dissertation
The kappa-opioid receptor in subregions of the nucleus accumbens shell in affective behavior and ethanol drinking
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2023
DOI:
https://doi.org/10.17918/00001957
Abstract
Alcohol use disorder commonly co-occurs with anxiety disorders. While the kappa-opioid receptor (KOR) has been implicated in both conditions, its manipulation has produced mixed effects. The KOR is densely expressed in the nucleus accumbens (NAc) shell, a region implicated in affective and motivated behavior, where studies of KOR agonism have found subregion-specific effects on affect but no effect on ethanol drinking. This thesis examined the effects of KOR agonism in subregions of the NAc shell on affective behavior and ethanol drinking. Stimulation of the KOR in the caudal NAc shell of male rats promoted anxiety-like behavior and inhibited dopamine release, while stimulation in the rostral shell instead reduced anxiety-like behavior and inhibited dopamine release to a lesser extent. Examining sex-related differences in ethanol drinking, half of female rats consumed significantly higher levels of ethanol than the other females and almost all males, but females and males displayed similar effects of ethanol drinking on affective behavior. Agonism of the KOR in the caudal NAc shell also increased ethanol drinking in both males and high-drinking females, while agonism in the rostral shell instead decreased ethanol intake in males and low-drinking females but increased it in high-drinking females. These results demonstrate that the KOR can have differential effects on dopamine release, affective behavior, and ethanol drinking, depending on the NAc shell subregion targeted and the subject sex and level of ethanol drinking. This suggests that sex or drinking phenotype may predict the effectiveness of certain KOR-based medications for anxiety and alcohol use disorders.
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Details
- Title
- The kappa-opioid receptor in subregions of the nucleus accumbens shell in affective behavior and ethanol drinking
- Creators
- Breanne Elizabeth Pirino
- Contributors
- Jessica R. Barson (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- ix, 152 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Other Identifier
- 991021819015204721