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- All Subjects: psychology
- All Subjects: Diabetes
- Creators: Sanabria, Federico
- Creators: Johnston, Carol
Description
Nicotine is thought to underlie the reinforcing and dependence-producing effects of tobacco-containing products. Nicotine supports self-administration in rodents, although measures of its reinforcing effects are often confounded by procedures that are used to facilitate acquisition, such as food restriction, prior reinforcement training, or response-contingent co-delivery of a naturally reinforcing light. This study examined whether rats acquire nicotine self-administration in the absence of these facilitators. A new mathematical modeling procedure was used to define the criterion for acquisition and to determine dose-dependent differences in rate and asymptote levels of intake. Rats were trained across 20 daily 2-h sessions occurring 6 days/week in chambers equipped with active and inactive levers. Each active lever press resulted in nicotine reinforcement (0, 0.015, 0.03, 0.06 mg/kg, IV) and retraction of both levers for a 20-s time out, whereas inactive lever presses had no consequences. Acquisition was defined by the best fit of a logistic function (i.e., S-shaped) versus a constant function (i.e., flat line) for reinforcers obtained across sessions using a corrected Akaike information criterion (AICc) as a model selection tool. The results showed an inverted-U shaped function for dose in relation to the percentage of animals that acquired nicotine self-administration, with 46% acquiring at 0.015 mg/kg, 73% at 0.03 mg/kg, and 58% at 0.06 mg/kg. All saline rats failed to acquire as expected. For rats that acquired nicotine self-administration, multiple model comparisons demonstrated that the asymptote (highest number of reinforcers/session) and half learning point (h; session during which half the assymptote had been achieved) were justified as free parameters of the reinforcers/session function, indicating that these parameters vary with nicotine dose. Asymptote exhibited an inverted U-shaped function across doses and half learning point exhibited a negative relationship to dose (i.e., the higher the dose the fewer sessions to reach h). These findings suggest that some rats acquire nicotine self-administration without using procedures that confound measures of acquisition rate. Furthermore, the modeling approach provides a new way of defining acquisition of drug self-administration that takes advantage of using all data generated from individual subjects and is less arbitrary than some criteria that are currently used.
ContributorsCole, Natalie (Author) / Neisewander, Janet L (Thesis advisor) / Sanabria, Federico (Thesis advisor) / Bimonte-Nelson, Heather A. (Committee member) / Olive, Michael F (Committee member) / Arizona State University (Publisher)
Created2011
Description
The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex (mPFC), and amygdala, are of special interest due to documented structural changes and their implication in post-traumatic stress disorder (PTSD). One of many notable chronic stress-induced changes include dendritic arbor restructuring, which reflect plasticity patterns in parallel with the direction of alterations observed in functional imaging studies in PTSD patients. For instance, chronic stress produces dendritic retraction in the hippocampus and mPFC, but dendritic hypertrophy in the amygdala, consistent with functional imaging in patients with PTSD. Some have hypothesized that these limbic region's modifications contribute to one's susceptibility to develop PTSD following a traumatic event. Consequently, we used a familiar chronic stress procedure in a rat model to create a vulnerable brain that might develop traits consistent with PTSD when presented with a challenge. In adult male rats, chronic stress by wire mesh restraint (6h/d/21d) was followed by a variety of behavioral tasks including radial arm water maze (RAWM), fear conditioning and extinction, and fear memory reconsolidation to determine chronic stress effects on behaviors mediated by these limbic structures. In chapter 2, we corroborated past findings that chronic stress caused hippocampal CA3 dendritic retraction. Importantly, we present new findings that CA3 dendritic retraction corresponded with poor spatial memory in the RAWM and that these outcomes reversed after a recovery period. In chapter 3, we also showed that chronic stress impaired mPFC-mediated extinction memory, findings that others have reported. Using carefully assessed behavior, we present new findings that chronic stress impacted nonassociative fear by enhancing contextual fear during extinction that generalized to a new context. Moreover, the generalization behavior corresponded with enhanced functional activation in the hippocampus and amygdala during fear extinction memory retrieval. In chapter 5, we showed for the first time that chronic stress enhanced amygdala functional activation during fear memory retrieval, i.e., reactivation. Moreover, these enhanced fear memories were resistant to protein synthesis interference to disrupt a previously formed memory, called reconsolidation in a novel attempt to weaken chronic stress enhanced traumatic memory. Collectively, these studies demonstrated the plastic and dynamic effects of chronic stress on limbic neurocircuitry implicated in PTSD. We showed that chronic stress created a structural and functional imbalance across the hippocampus, mPFC, and amygdala, which lead to a PTSD-like phenotype with persistent and exaggerated fear following fear conditioning. These behavioral disruptions in conjunction with morphological and functional imaging data reflect a chronic stress-induced imbalance between hippocampal and mPFC regulation in favor of amygdala function overdrive, and supports a novel approach for traumatic memory processing in PTSD.
ContributorsHoffman, Ann (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Hammer, Jr., Ronald P. (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2013
Description
There are several visual dimensions of food that can affect food intake, example portion size, color, and variety. This dissertation elucidates the effect of number of pieces of food on preference and amount of food consumed in humans and motivation for food in animals. Chapter 2 Experiment 1 showed that rats preferred and also ran faster for multiple pieces (30, 10 mg pellets) than an equicaloric, single piece of food (300 mg) showing that multiple pieces of food are more rewarding than a single piece. Chapter 2 Experiment 2 showed that rats preferred a 30-pellet food portion clustered together rather than scattered. Preference and motivation for clustered food pieces may be interpreted based on the optimal foraging theory that animals prefer foods that can maximize energy gain and minimize the risk of predation. Chapter 3 Experiment 1 showed that college students preferred and ate less of a multiple-piece than a single-piece portion and also ate less in a test meal following the multiple-piece than single-piece portion. Chapter 3 Experiment 2 replicated the results in Experiment 1 and used a bagel instead of chicken. Chapter 4 showed that college students given a five-piece chicken portion scattered on a plate ate less in a meal and in a subsequent test meal than those given the same portion clustered together. This is consistent with the hypothesis that multiple pieces of food may appear like more food because they take up a larger surface area than a single-piece portion. All together, these studies show that number and surface area occupied by food pieces are important visual cues determining food choice in animals and both food choice and intake in humans.
ContributorsBajaj, Devina (Author) / Phillips, Elizabeth D. (Thesis advisor) / Cohen, Adam (Committee member) / Johnston, Carol (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Objective: Vinegar consumption studies have demonstrated possible therapeutic effects in reducing HbA1c and postprandial glycemia. The purpose of the study was to closely examine the effects of a commercial vinegar drink on daily fluctuations in fasting glucose concentrations and postprandial glycemia, and on HbA1c, in individuals at risk for Type 2 Diabetes Mellitus (T2D). Design: Thirteen women and one man (21-62 y; mean, 46.0±3.9 y) participated in this 12-week parallel-arm trial. Participants were recruited from a campus community and were healthy and not diabetic by self-report. Participants were not prescribed oral hypoglycemic medications or insulin; other medications were allowed if use was stable for > 3 months. Subjects were randomized to one of two groups: VIN (8 ounces vinegar drink providing 1.5 g acetic acid) or CON (1 vinegar pill providing 0.04 g acetic acid). Treatments were taken twice daily immediately prior to the lunch and dinner meals. Venous blood samples were drawn at trial weeks 0 and 12 to measure insulin, fasting glucose, and HbA1c. Subjects recorded fasting glucose and 2-h postprandial glycemia concentrations daily using a glucometer. Results: The VIN group showed significant reductions in fasting capillary blood glucose concentrations (p=0.05) that were immediate and sustained throughout the duration of the study. The VIN group had reductions in 2-h postprandial glucose (mean change of −7.6±6.8 mg/dL over the 12-week trial), but this value was not significantly different than that for the CON group (mean change of 3.3±5.3 mg/dL over the 12-week trial, p=0.232). HbA1c did not significantly change (p=0.702), but the reduction in HbA1c in the VIN group, −0.14±0.1%, may have physiological relevance. Conclusions: Significant reductions in HbA1c were not observed after daily consumption of a vinegar drink containing 1.5 g acetic acid in non-diabetic individuals. However, the vinegar drink did significantly reduce fasting capillary blood glucose concentrations in these individuals as compared to a vinegar pill containing 0.04 g acetic acid. These results support a therapeutic effect for vinegar in T2D prevention and progression, specifically in high-risk populations.
ContributorsQuagliano, Samantha (Author) / Johnston, Carol (Thesis advisor) / Appel, Christy (Committee member) / Dixon, Kathleen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Each year, millions of aging women will experience menopause, a transition from reproductive capability to reproductive senescence. In women, this transition is characterized by depleted ovarian follicles, declines in levels of sex hormones, and a dysregulation of gonadotrophin feedback loops. Consequently, menopause is accompanied by hot flashes, urogenital atrophy, cognitive decline, and other symptoms that reduce quality of life. To ameliorate these negative consequences, estrogen-containing hormone therapy is prescribed. Findings from clinical and pre-clinical research studies suggest that menopausal hormone therapies can benefit memory and associated neural substrates. However, findings are variable, with some studies reporting null or even detrimental cognitive and neurobiological effects of these therapies. Thus, at present, treatment options for optimal cognitive and brain health outcomes in menopausal women are limited. As such, elucidating factors that influence the cognitive and neurobiological effects of menopausal hormone therapy represents an important need relevant to every aging woman. To this end, work in this dissertation has supported the hypothesis that multiple factors, including post-treatment circulating estrogen levels, experimental handling, type of estrogen treatment, and estrogen receptor activity, can impact the realization of cognitive benefits with Premarin hormone therapy. We found that the dose-dependent working memory benefits of subcutaneous Premarin administration were potentially regulated by the ratios of circulating estrogens present following treatment (Chapter 2). When we administered Premarin orally, it impaired memory (Chapter 3). Follow-up studies revealed that this impairment was likely due to the handling associated with treatment administration and the task difficulty of the memory measurement used (Chapters 3 and 4). Further, we demonstrated that the unique cognitive impacts of estrogens that become increased in circulation following Premarin treatments, such as estrone (Chapter 5), and their interactions with the estrogen receptors (Chapter 6), may influence the realization of hormone therapy-induced cognitive benefits. Future directions include assessing the mnemonic effects of: 1) individual biologically relevant estrogens and 2) clinically-used bioidentical hormone therapy combinations of estrogens. Taken together, information gathered from these studies can inform the development of novel hormone therapies in which these parameters are optimized.
ContributorsEngler-Chiurazzi, Elizabeth (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Sanabria, Federico (Committee member) / Olive, Michael F (Committee member) / Hoffman, Steven (Committee member) / Arizona State University (Publisher)
Created2013
Description
When a rolling ball exits a spiral tube, it typically maintains its final inertial state and travels along straight line in concordance with Newton's first law of motion. Yet, most people predict that the ball will curve, a "naive physics" misconception called the curvilinear impetus (CI) bias. In the current paper, we explore the ecological hypothesis that the CI bias arises from overgeneralization of correct motion of biological agents. Previous research has established that humans curve when exiting a spiral maze, and college students believe this motion is the same for balls and humans. The current paper consists of two follow up experiments. The first experiment tested the exiting behavior of rodents from a spiral rat maze. Though there were weaknesses in design and procedures of the maze, the findings support that rats do not behave like humans who exhibit the CI bias when exiting a spiral maze. These results are consistent with the CI bias being an overgeneralization of human motion, rather than generic biological motion. The second experiment tested physics teachers on their conception of how a humans and balls behave when exiting a spiral tube. Teachers demonstrated correct knowledge of the straight trajectory of a ball, but generalized the ball's behavior to human motion. Thus physics teachers exhibit the opposite bias from college students and presume that all motion is like inanimate motion. This evidence supports that this type of naive physics inertial bias is at least partly due to participants overgeneralizing both inanimate and animate motion to be the same, perhaps in an effort to minimize cognitive reference memory load. In short, physics training appears not to eliminate the bias, but rather to simply shift it from the presumption of stereotypical animate to stereotypical inanimate behavior.
ContributorsDye, Rosaline (Author) / Mcbeath, Michael K (Thesis advisor) / Sanabria, Federico (Committee member) / Megowan, Colleen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Anxiety sensitivity (AS; the fear of anxiety-related bodily sensations) has been earmarked as a significant risk factor in the development and maintenance of pathological anxiety in adults and children. Given the potential implications of heightened AS, recent research has focused on investigating the etiology and developmental course of elevated AS; however, most of this work has been conducted with adults and is retrospective in nature. Data from college students show that early anxiety-related learning experiences may be a primary source of heightened AS levels, but it remains unclear whether AS in children is linked to their learning experiences (i.e., parental reinforcement, modeling, punishment, and/or transmission of information about anxiety-related behaviors). Based on AS theory and its iterations, an emerging theoretical model was developed to aid further exploration of the putative causes and consequences of heightened AS levels. Using a sample of 70 clinic-referred youth (ages 6 to 16 years old; 51.4% Hispanic/Latino), the present study sought to further explicate the role of learning in the development of AS and anxiety symptoms. Results suggest that childhood learning experiences may be an important precursor to heightened AS levels and, subsequently, increased experiences of anxiety symptoms. Findings also indicate that some youth may be more vulnerable to anxiety-related learning experiences and suggest that culture may play a role in the relations among learning, AS, and anxiety symptoms.
ContributorsHolly, Lindsay (Author) / Pina, Armando A (Thesis advisor) / Crnic, Keith A (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2012
Description
The unpleasant bitter taste found in many nutritious vegetables may deter people from consuming a healthy diet. We investigated individual differences in taste perception and whether these differences influence the effectiveness of bitterness masking. To test whether phenylthiocarbamide (PTC) `supertasters' also taste salt and sugar with greater intensity, as suggested by Bartoshuk and colleagues (2004), we infused strips of paper with salt water or sugar water. The bitterness rating of the PTC strip had a significant positive linear relationship with ratings of both the intensity of sweet and salt, but the effect sizes were very low, suggesting that the PTC strip does not give a complete picture of tasting ability. Next we investigated whether various seasonings could mask the bitter taste of vegetables and whether this varied with tasting ability. We found that sugar decreased bitterness and lemon decreased liking for vegetables of varying degrees of bitterness. The results did not differ by ability to taste any of the flavors. Therefore, even though there are remarkable individual differences in taste perception, sugar can be used to improve the initial palatability of vegetables and increase their acceptance and consumption.
ContributorsWilkie, Lynn Melissa (Author) / Phillips, Elizabeth D. (Thesis advisor) / Cohen, Adam (Committee member) / Johnston, Carol (Committee member) / Arizona State University (Publisher)
Created2012
Description
Many people with or at risk for diabetes have difficulty maintaining normal postprandial blood glucose levels (120-140 mg/dl). Research has shown that vinegar decreases postprandial glycemia. The purpose of this study was to examine a possible mechanism by which vinegar decreases postprandial glycemia, particularly the effect of vinegar ingestion on gut fermentation. In this parallel arm randomized control trial, the effects of daily ingestion of vinegar on gut fermentation markers were observed among adults at risk for type 2 diabetes in Phoenix, Arizona. Subjects (n=14) were randomly assigned to treatments consisting of a vinegar drink (1.5g acetic acid) or a placebo (2 vinegar pills containing 40mg acetic acid each). All participants were required to consume the vinegar drink (16 oz) or 2 placebo pills every day for 12 weeks. At week 12, participants filled out a questionnaire to report gastrointestinal (GI) symptoms and three consecutive breath samples were taken from each subject to measure fasting breath hydrogen (BH2) with a breath analyzer. Fasting BH2 measures for the vinegar drink group (16.1+11.8 ppm) were significantly different than those from the pill group (3.6+1.4) with a partial eta squared of 0.39 (p=0.023). After adjusting for age as a confounding factor (r=0.406) and removing an outlier, fasting BH2 measures for the vinegar drink group (4.3+1.1 ppm) were still significantly different than those from the pill group (3.6+1.4) with a partial eta squared of 0.35 (p=0.045). Participants in both groups reported mild changes in GI symptoms. In conclusion, adults at risk for type 2 diabetes that consume 2 tablespoons of vinegar a day may have increased gut fermentation compared to those who do not consume vinegar.
ContributorsWhite, Serena (Author) / Johnston, Carol (Thesis advisor) / Appel, Christy (Committee member) / Martin, Keith (Committee member) / Arizona State University (Publisher)
Created2013
Description
ABSTRACT This randomized, controlled, double-blind crossover study examined the effects of a preprandial, 20g oral dose of apple cider vinegar (ACV) on colonic fermentation and glycemia in a normal population, with the ultimate intention of identifying the mechanisms by which vinegar has been shown to reduce postprandial glycemia and insulinemia. Fifteen male and female subjects were recruited, ages 20-60y, who had no prior history of gastrointestinal (GI) disease or resections impacting normal GI function, were non-smokers, were non-vegetarian/vegan, were not taking any medications known to alter (glucose) metabolism, and were free of chronic disease including diabetes. Subjects were instructed to avoid exercise, alcohol and smoking the day prior to their trials and to consume a standardized, high-carbohydrate dinner meal the eve prior. There was a one-week washout period per subject between appointments. Breath hydrogen, serum insulin and capillary glucose were assessed over 3 hours after a high-starch breakfast meal to evaluate the impact of preprandial supplementation with ACV or placebo (water). Findings confirmed the antiglycemic effects of ACV as documented in previous studies, with significantly lower mean blood glucose concentrations observed during ACV treatment compared to the placebo at 30 min (p=0.003) and 60 min (p=0.005), and significantly higher mean blood glucose concentrations at 180 min (p=0.045) postprandial. No significant differences in insulin concentrations between treatments. No significant differences were found between treatments (p>0.05) for breath hydrogen; however, a trend was observed between the treatments at 180 min postprandial where breath hydrogen concentration was visually perceived as being higher with ACV treatment compared to the placebo. Therefore, this study failed to support the hypothesis that preprandial ACV ingestion produces a higher rate of colonic fermentation within a 3 hour time period following a high-carbohydrate meal. Due to variations in experiment duration noted in other literature, an additional study of similar nature with an expanded specimen collections period, well beyond 3 hours, is warranted.
ContributorsMedved, Emily M (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2012