Thesis
THE IMPACT OF PRENATAL EXPOSURE TO INFECTION ON LATER-LIFE ALCOHOL USE
Washington State University
Master of Science (MS), Washington State University
12/2024
DOI:
https://doi.org/10.7273/000007214
Abstract
Prenatal exposure to infection is a risk factor in the development of several neuropsychiatric disorders, including schizophrenia and depression. These disorders often co-occur with alcohol misuse which leads to adverse outcomes, including increased hospitalization and mortality. Despite these consequences, little is understood regarding the mechanisms regarding how early exposure to infection impacts brain development, which inhibits our ability to create effective therapies. We have previously demonstrated that maternal immune activation (MIA), a model of prenatal exposure to infection, combined with adolescent alcohol exposure (AE) leads to enhanced home-cage drinking and disrupts cortical-striatal oscillations in adult offspring. The current project aims to determine whether these findings extend to operant alcohol self-administration, and whether the anti-oxidant n-acetylcysteine (NAC) may be effective in preventing the effect of MIA on drinking behavior. Pregnant Sprague-Dawley rats were exposed to poly(I:C) (4mg/kg) or saline on gestational day 15 and were exposed to NAC (100 mg/kg) or saline 24 hours before and after MIA treatment. During adolescence, postnatal day (PD) 28-48,
offspring were given 24-hour home cage access to 10% ethanol (AE) using a two-bottle choice technique. In adulthood (>PD 70), rats were trained to self-administer 10% ethanol for 30-minutes, 5 days per week. The results of this study show that MIA/AE increases alcohol self-administration, as measured by active lever presses and mean alcohol consumed (g/kg). This effect was more pronounced in males. Furthermore, prenatal NAC treatment prevented these increases in alcohol self-administration. These data contribute to our overall hypothesis that oxidative stress caused by MIA negatively influences synaptic development, which primes the brain to be more susceptible to the negative effects of AE, leading to increases in alcohol drinking behavior in adulthood. Ongoing work attempts to identify whether/how MIA and AE impacts synaptic plasticity in rodents, in order to determine the physical mechanism that underlies the behavioral changes we observed here. Therefore, future studies will investigate the impact of MIA and AE on dendritic spine, microglia and astrocyte densities.
Metrics
2 File views/ downloads
4 Record Views
Details
- Title
- THE IMPACT OF PRENATAL EXPOSURE TO INFECTION ON LATER-LIFE ALCOHOL USE
- Creators
- Skylar E. Nicholson
- Contributors
- Angela M. Henricks (Chair)Kimberly Meidenbauer (Committee Member)Kristen Delevich (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Department of Psychology
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 58
- Identifiers
- 99901195439001842
- Language
- English
- Resource Type
- Thesis