Dissertation
Regulation of excessive alcohol consumption by the neurotensin system in the paraventricular thalamus
Doctor of Philosophy (Ph.D.), Drexel University
Nov 2019
DOI:
https://doi.org/10.17918/wkf1-rv30
Abstract
A subset of the alcohol drinking population engages in excessive alcohol consumption, placing themselves at risk for serious health consequences. A better understanding of the psychobiological mechanisms that propel these individuals both to initiate and perpetuate excessive drinking may help identify new targets for therapeutic interventions. Using a rat model of voluntary alcohol drinking, we found that individuals showing greater risk-taking behavior prior to any alcohol consumption went on to engage in excessive alcohol drinking. Moreover, these individuals exhibited lower gene expression and peptide levels of the neuropeptide-neurotensin-in the posterior paraventricular thalamus (pPVT). This neurochemical signature in the vulnerable individuals was found to directly influence both their risk-taking behavior and their alcohol drinking, as raising neurotensin levels in the pPVT suppressed both behaviors. Chronic alcohol drinking led excessive drinkers to exhibit heightened levels of risky exploration and, concurrently, elevated levels of the neurotensin receptor 2 (NTSR2) in the anterior paraventricular thalamus (aPVT). Increasing NTSR2 signaling in the aPVT of low alcohol drinkers increased their risky exploration, suggesting that the neurotensin system in the aPVT also contributes to risk-taking behavior. Together, these findings suggest that the neurotensin system in the pPVT contributes to the initial vulnerability to excessive drinking, whereas the neurotensin system in the aPVT mediates a chronic alcohol-induced behavioral phenotype representing a later stage vulnerability to excessive drinking. Thus, the PVT neurotensin system may be an important target for the prevention and treatment of excessive alcohol consumption at different stages of the alcohol drinking trajectory.
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Details
- Title
- Regulation of excessive alcohol consumption by the neurotensin system in the paraventricular thalamus
- Creators
- Surya Pandey - DU
- Contributors
- Jessica R. Barson (Advisor) - Drexel University (1970-)Ramesh Raghupathi (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- x, 163 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 11373; 991014632326204721