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Description
Substance abuse disorder is a debilitating condition characterized by recurring drug-seeking behaviors and high rates of relapse. In male rats, this tendency to engage in drug-seeking behavior can be inhibited by environmental enrichment (EE) during abstinence. We have shown previously that cocaine-seeking behavior is associated with an increase in addiction-related genes such as Arc and CamkIIa and a decrease in the microRNA miR-495. We have also shown that miR-495 inhibits expression of Arc and CamkIIa post-transcriptionally. Therefore, we hypothesize that reduced cocaine-seeking behavior in EE female rats is associated with a downregulation of these addiction-related genes as well as an upregulation of miR-495 in the NAc shell. Based on previous studies that highlight differences between male and female motivation for cocaine, we also hypothesize that EE will not affect female motivation for cocaine as robustly as males. After acquiring cocaine through self-administration, females were assigned to either an enriched environment (EE) condition or an isolated condition, where they remained during abstinence. They were then given a one-hour cue-reactivity test, during which cocaine-seeking behavior differed significantly between the EE and isolated groups. We also found that the addiction-related genes Arc and CamkIIa were downregulated in the NAc core of EE females. Future research is needed to examine the role of miR-495 in these changes in behavior and gene expression. Overall, the results suggest that EE is protective against relapse to cocaine-seeking in females and may normalize the dysregulation of genes by cocaine.
ContributorsSt Peter, Madeleine Kay (Author) / Neisewander, Janet (Thesis director) / Newbern, Jason (Committee member) / Powell, Gregory (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Traumatic brain injury (TBI)—sudden impact or acceleration trauma to the head—is a major cause of death and disability worldwide and is particularly amplified in pediatric cases. TBI is the leading cause of mortality and morbidity in children and adolescents. Adolescence is a critical time where the brain undergoes cognitive development and brain injury-induced disruptions to these processes can lead to life-long debilitating morbidities. The aim of this study was to determine if exercising spatial and contextual memory circuits using a novel rehabilitation strategy called Peg Forest Rehabilitation (PFR) could mitigate the onset of injury-induced cognitive deficits in juvenile rats subjected to diffuse TBI. The PFR aims to synthesize neuroplasticity-based enrichment to improve cognitive outcomes after TBI. We hypothesized that PFR treatment would mitigate the onset of brain injury-induced cognitive deficits and reduce neuroinflammation. Juvenile male Sprague-Dawley rats (post-natal day 35) were subjected to diffuse traumatic brain injury via midline fluid percussion injury or a control surgery. One-week post-injury, rats were exposed to PFR or cage control exploration (15 min/day). PFR allowed free navigation through random configuration of the peg-filled arena for 10 days over 2 weeks. Control rats remained in home cages in the center of the arena with the peg-board removed for 15 min/day/10 days. One-week post-rehabilitation (one-month post-injury), cognitive performance was assessed for short-term (novel object recognition; NOR), long-term (novel location recognition; NLR), and working (temporal order recognition; TOR) memory performance, calculated as a discrimination index between novel and familiar objects. Tissue was collected for immunohistochemistry and stained for ionized calcium binding proteins (Iba-1) to visualize microglia morphology, and somatostatin. PFR attenuated TBI-induced deficits on the NOR task, where the TBI-PFR treatment group spent significantly more time with the novel object compared with the familiar (*p=0.0046). Regardless of rehabilitation, brain-injured rats had hyper-ramified microglia in the hypothalamus indicated by longer branch lengths and more endpoints per cell compared with uninjured shams. Analysis of somatostatin data is ongoing. In this study, passive, intermittent PFR that involved dynamic, novel spatial navigation, prevented TBI-induced cognitive impairment in adolescent rats. Spatial navigation training may have clinical efficacy and should be further investigated.
ContributorsAftab, Umar (Author) / Rowe, Rachel K. (Thesis director) / Newbern, Jason M. (Thesis director) / Ortiz, J. Bryce (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05