Dissertation
Sex-specific chronic behavioral deficits following mild traumatic brain injury in the adolescent rat
Doctor of Philosophy (Ph.D.), Drexel University
Aug 2018
DOI:
https://doi.org/10.17918/58pp-z161
Abstract
Following mild TBI, girls report more emotional symptoms and take longer to recover from their symptoms than boys. Thirty five-day-old male and female rats were used to model mild TBI in the adolescent human. Female, but not male, adolescent rats subjected to this mild TBI exhibit depression-like behavior using the forced swim test (FST) at 5-6 weeks post-injury during the estrus phase of the estrous cycle. The dopaminergic system has been implicated in depression-like behavior and chronic alterations in dopaminergic neurotransmission, suggestive of a state of hypodopaminergia, have been reported following moderate-severe TBI. We hypothesized that impairments in dopaminergic neurotransmission may contribute to depression-like behavior as ventral tegmental area (VTA) neurons of brain-injured rats exhibited evidence of reduced activity. DREADD-mediated activation of dopaminergic neurons in the VTA was able to reverse the brain injury-induced depression-like behavior. This effect appeared to be mediated via dopamine D2-like receptors as this effect could be mimicked by administration of the dopamine D2-like receptor agonist, quinpirole. Estrogen receptor antagonist, tamoxifen, and progesterone receptor antagonist, mifepristone, administration during proestrus prevented the depression-like behavior in estrus. Taken together, this data suggests that mild TBI-induced reductions in activity of VTA neurons in combination with estrous phase-dependent surges in circulating hormones may contribute to depression-like behavior in female rats.
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Details
- Title
- Sex-specific chronic behavioral deficits following mild traumatic brain injury in the adolescent rat
- Creators
- Laura Giacometti - DU
- Contributors
- Ramesh Raghupathi (Advisor) - Drexel University (1970-)Sandhya Kortagere (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xx, 237 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Other Identifier
- 8851; 991014632216904721