Dissertation
The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in alcohol drinking
Doctor of Philosophy (Ph.D.), Drexel University
Nov 2019
DOI:
https://doi.org/10.17918/5ckk-0f46
Abstract
Excessive alcohol intake is a leading preventable cause of death in the United States, but currently available pharmacological treatments are not widely effective. Better understanding of the neurobiological mechanisms underlying this disorder may help identify new targets for the development of effective treatments. Very limited evidence has suggested that the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), may play a role in ethanol drinking, but the brain regions and protein isoforms involved remain to be determined. This thesis explores the role of the two PACAP isoforms, PACAP-27 and PACAP-38, in two brain regions that may be crucially involved in ethanol intake. In the thalamic paraventricular nucleus (PVT), a major node in the limbic system, PACAP-27 was identified in nearly half of all cells and showed increased levels in individual cells of the PVT following binge-like consumption of ethanol. With the PVT known to have dense projections to the nucleus accumbens (NAc), PACAP-27 was identified in a majority of PVT afferents to the NAc shell. Within the NAc shell, PACAP-27 but not PACAP-38 selectively reduced binge-like ethanol drinking. This effect was both substance- and subregion-specific and did not involve stress-related behaviors. Together, these results suggest that, following an ethanol binge, levels of PACAP-27 are released from the PVT to the NAc shell to serve as a 'stop-signal' for ethanol drinking. By providing insight into the role of the PACAP isoforms in ethanol drinking, the findings from this thesis suggest that PACAP-27 may represent a novel therapeutic target for treating alcohol use disorder.
Metrics
57 File views/ downloads
41 Record Views
Details
- Title
- The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in alcohol drinking
- Creators
- Andrew Thomas Gargiulo - DU
- Contributors
- Jessica R. Barson (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- ix, 120 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Other Identifier
- 11357; 991014632550804721