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Dissertation
The PACAP system and its effect on ethanol consumption: changes between non-dependent and dependent states
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2025
DOI:
https://doi.org/10.17918/00011346
Abstract
Alcohol use disorder is a major public health issue, but available pharmacotherapeutic medications are not widely effective. The identification of new medication targets could allow for the development of more effective treatments. Evidence suggests that the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), participates in alcohol consumption. According to the "dark side of addiction" hypothesis, the development of alcohol dependence involves an increased involvement of stress-related neuropeptides in the limbic system. Notably, PACAP is a stress peptide that is densely expressed in cells of the limbic paraventricular thalamus (PVT). This thesis explores the role of PVT PACAP in ethanol drinking in non-dependent and dependent states. In non-dependent rats, over-expression of PACAP in the PVT selectively prevented an escalation of ethanol binge drinking across weeks, with minimal effects on affective behavior. While activation of PACAP⁺ cells in the PVT also attenuated binge drinking in non-dependent mice, it instead increased it in dependent mice. With the PVT having dense projections to the nucleus accumbens (NAc), activation of PVT->NAc PACAP⁺ cells similarly increased binge drinking in dependent mice. Moreover, dependent mice showed upregulated gene expression of PACAP in the PVT, and a specific PACAP receptor variant in the NAc. Notably, knockdown of this variant decreased the elevated drinking of dependent mice, suggesting that this variant may be a mechanism through which ethanol drinking is increased in ethanol dependence. These findings implicate the PVT->NAc PACAP system as a possible key substrate influencing alcohol consumption both before and after the development of ethanol dependence.
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Details
- Title
- The PACAP system and its effect on ethanol consumption
- Creators
- Brody Allen Carpenter
- Contributors
- Jessica R. Barson (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University
- Number of pages
- vii, 113 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991022176376004721