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Description
Long term high fat diets (HFD) are correlated with the development of diabetes

and kidney disease. However, the impact of short term high fat intake on the etiology of kidney disease has not been well-studied. Therefore, this study examined the impact of a six week HFD (60% fat) on kidney structure

Long term high fat diets (HFD) are correlated with the development of diabetes

and kidney disease. However, the impact of short term high fat intake on the etiology of kidney disease has not been well-studied. Therefore, this study examined the impact of a six week HFD (60% fat) on kidney structure and function in young male Sprague-Dawley rats. Previous studies have shown that these animals develop indices of diabetes compared to rats fed a standard rodent chow (5% fat) for six weeks. The hypothesis of this study is that six weeks of HFD will lead to early stages of kidney disease as evidenced by morphological and functional changes in the kidney. Alterations in morphology were determined by measuring structural changes in the kidneys (changes in mass, fatty acid infiltration, and structural damage). Alterations in kidney function were measured by analyzing urinary biomarkers of oxidative RNA/DNA damage, renal tissue lipid peroxidation, urinary markers of impaired kidney function (urinary protein, creatinine, and hydrogen peroxide (H2O2)), markers of inflammation (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6)), as well as cystatin C, a plasma biomarker of kidney function. The results of these studies determined that short term HFD intake is not sufficient to induce early stage kidney disease. Beyond increases in renal mass, there were no significant differences between the markers of renal structure and function in the HFD and standard rodent chow-fed rats.
ContributorsCrinigan, Catherine (Author) / Sweazea, Karen (Thesis advisor) / Johnston, Carol (Committee member) / Mayol-Kreiser, Sandra (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Smoking remains the leading cause of preventable death in the United States, and early initiation is associated with greater difficulty quitting. Among adolescent smokers, those with attention-deficit hyperactivity disorder (ADHD), characterized by difficulties associated with impulsivity, hyperactivity, and inattention, smoke at nearly twice the rate of their peers.

Smoking remains the leading cause of preventable death in the United States, and early initiation is associated with greater difficulty quitting. Among adolescent smokers, those with attention-deficit hyperactivity disorder (ADHD), characterized by difficulties associated with impulsivity, hyperactivity, and inattention, smoke at nearly twice the rate of their peers. Although cigarette smoking is highly addictive, nicotine is a relatively weak primary reinforcer, spurring research on other potential targets that may maintain smoking, including the potential benefits of nicotine on attention, inhibition, and reinforcer efficacy. The present study employs the most prevalent rodent model of ADHD, the spontaneously hypertensive rat (SHR) and its control comparison Wistar Kyoto (WKY) to examine the effects of acute and chronic subcutaneous nicotine injections on performance in three operant response inhibition paradigms. Functional activation in select regions of the prefrontal cortex and striatum was also explored. Acute (0.1, 0.3, 0.6 mg/kg) and chronic (0.3 mg/kg) nicotine increased impulsive responding regardless of strain, dose, or operant schedule. Dose-dependent decreases in latency to initiate the task were also observed. SHR receiving daily nicotine injections showed less activation in the nucleus accumbens shell compared to saline controls. Despite close similarities, one of the three operant tasks did not detect response inhibition deficits in SHR relative to WKY. A closer examination of these tasks may highlight critical components involved in the amelioration of response inhibition deficits.
ContributorsMazur, Gabriel Joseph (Author) / Sanabria, Federico (Thesis advisor) / Killeen, Peter R (Committee member) / Neisewander, Janet L (Committee member) / Wynne, Clive DL (Committee member) / Arizona State University (Publisher)
Created2014
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Description
The failure to withhold inappropriate behavior is a central component of most impulse control disorders, including Attention Deficit Hyperactivity Disorder (ADHD). The present study examined the effects of housing environment and methylphenidate (a drug often prescribed for ADHD) on the performance of rats in two response inhibition tasks: differential reinforcement

The failure to withhold inappropriate behavior is a central component of most impulse control disorders, including Attention Deficit Hyperactivity Disorder (ADHD). The present study examined the effects of housing environment and methylphenidate (a drug often prescribed for ADHD) on the performance of rats in two response inhibition tasks: differential reinforcement of low rate (DRL) and fixed minimum interval (FMI). Both tasks required rats to wait a fixed amount of time (6 s) before emitting a reinforced response. The capacity to withhold the target response (volitional inhibition) and timing precision were estimated on the basis of performance in each of the tasks. Paradoxically, rats housed in a mildly enriched environment that included a conspecific displayed less volitional inhibition in both tasks compared to rats housed in an isolated environment. Enriched housing, however, increased timing precision. Acute administration of methylphenidate partially reversed the effects of enriched housing. Implications of these results in the assessment and treatment of ADHD-related impulsivity are discussed.
ContributorsHill, Jade C (Author) / Sanabria, Federico (Thesis advisor) / Killeen, Peter (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2011
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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.

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
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Description
Theories of interval timing have largely focused on accounting for the aggregate properties of behavior engendered by periodic reinforcement, such as sigmoidal psychophysical functions and their scalar property. Many theories of timing also stipulate that timing and motivation are inseparable processes. Such a claim is challenged by fluctuations in and

Theories of interval timing have largely focused on accounting for the aggregate properties of behavior engendered by periodic reinforcement, such as sigmoidal psychophysical functions and their scalar property. Many theories of timing also stipulate that timing and motivation are inseparable processes. Such a claim is challenged by fluctuations in and out of states of schedule control, making it unclear whether motivation directly affects states related to timing. The present paper seeks to advance our understanding of timing performance by analyzing and comparing the distribution of latencies and inter-response times (IRTs) of rats in two fixed-interval (FI) schedules of food reinforcement (FI 30-s and FI 90-s), and in two levels of food deprivation. Computational modeling revealed that each component was well described by mixture probability distributions embodying two-state Markov chains. Analysis of these models revealed that only a subset of latencies are sensitive to the periodicity of reinforcement, and pre-feeding only reduces the size of this subset. The distribution of IRTs suggests that behavior in FI schedules is organized in bouts that lengthen and ramp up in frequency with proximity to reinforcement. Pre-feeding slowed down the lengthening of bouts and increased the time between bouts. When concatenated, these models adequately reproduced sigmoidal FI response functions. These findings suggest that behavior in FI fluctuates in and out of schedule control; an account of such fluctuation suggests that timing and motivation are dissociable components of FI performance. These mixture-distribution models also provide novel insights on the motivational, associative, and timing processes expressed in FI performance, which need to be accounted for by causal theories of interval timing.
ContributorsDaniels, Carter W (Author) / Sanabria, Federico (Thesis advisor) / Brewer, Gene (Committee member) / Wynne, Clive (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Many behaviors are organized into bouts – brief periods of responding punctuated by pauses. This dissertation examines the operant bouts of the lever pressing rat. Chapter 1 provides a brief history of operant response bout analyses. Chapters 2, 3, 5, and 6 develop new probabilistic models to identify changes in

Many behaviors are organized into bouts – brief periods of responding punctuated by pauses. This dissertation examines the operant bouts of the lever pressing rat. Chapter 1 provides a brief history of operant response bout analyses. Chapters 2, 3, 5, and 6 develop new probabilistic models to identify changes in response bout parameters. The parameters of those models are demonstrated to be uniquely sensitive to different experimental manipulations, such as food deprivation (Chapters 2 and 4), response requirements (Chapters 2, 4, and 5), and reinforcer availability (Chapters 2 and 3). Chapter 6 reveals the response bout parameters that underlie the operant hyperactivity of a common rodent model of attention deficit hyperactivity disorder (ADHD), the spontaneously hypertensive rat (SHR). Chapter 6 then ameliorates the SHR’s operant hyperactivity using training procedures developed from findings in Chapters 2 and 4. Collectively, this dissertation provides new tools for the assessment of response bouts and demonstrates their utility for discerning differences between experimental preparations and animal strains that may be otherwise indistinguishable with more primitive methods.
ContributorsBrackney, Ryan J (Author) / Sanabria, Federico (Thesis advisor) / Smith, Brian H. (Thesis advisor) / Neisewander, Janet (Committee member) / Killeen, Peter (Committee member) / Arizona State University (Publisher)
Created2015
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Description
There has long been a link tied between obesity and such pathological conditions as nonalcoholic fatty liver disease and type two diabetes. Studies have shown that feeding rats a diet high in fat results in hepatic steatosis and steatohepatitis. Using a novel short term diet of six weeks with male

There has long been a link tied between obesity and such pathological conditions as nonalcoholic fatty liver disease and type two diabetes. Studies have shown that feeding rats a diet high in fat results in hepatic steatosis and steatohepatitis. Using a novel short term diet of six weeks with male adolescent Sprague-Dawley rats, our laboratory sought to investigate the early effects of high fat intake on the liver. Prior findings in our laboratory found that a high fat diet (HFD) leads to nonalcoholic fatty liver disease as well as other symptoms of metabolic syndrome. This study hypothesized that rats fed a 60% HFD for 6 weeks, unlike a high sucrose or standard chow diet, would have an elevated expression of pro-inflammatory cytokines associated with steatohepatitis. TNF-α, TLR4 and XBP1 were chosen for their link to hepatic inflammation. The results of this study found that contrary to the hypothesis, the high fat diet did not induce significant changes in the expression of any inflammatory marker in comparison to a high sucrose or control chow diet.
ContributorsCalhoun, Matthew (Author) / Sweazea, Karen (Thesis director) / Deviche, Pierre (Reviewer) / Barrett, The Honors College (Contributor)
Created2015-05
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Description
The purpose of the present study was to evaluate if the size of food items is an important dimension of food incentive in rats. The experiment involved training rats on a T-maze with 1, 45 mg pellet and 7, 5 mg pellets in one alternative and 8, 10 mg pellets

The purpose of the present study was to evaluate if the size of food items is an important dimension of food incentive in rats. The experiment involved training rats on a T-maze with 1, 45 mg pellet and 7, 5 mg pellets in one alternative and 8, 10 mg pellets in the other alternative. Results from this study indicated that the rats showed preference for the alternative that contained the 1, 45 mg pellet surrounded by 7, 5 mg pellets. Thus, rats preferred the food set that contained the larger sized food unit to an equicaloric food set with only smaller sized food units. In regards to running speed, no significant differences were found for either alternative of food. Results from this study indicated that the apparent size of an item could be a factor in the incentive value of food and perhaps, rats used size as a heuristic, placing a higher incentive value on the food set that contained the larger sized food unit than one containing only smaller sized food units.
ContributorsAnderson, Ashley Linnea (Author) / Phillips, Elizabeth Capaldi (Thesis director) / Presson, Clark (Committee member) / Cohen, Adam (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2013-05
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Description
High fat diets (HFD) are known to cause hepatic non-alcoholic steatosis in rats in as few as four weeks. Accumulation of triglycerides in liver and skeletal muscle is associated with insulin resistance and obesity. However, studies of fat accumulation in cardiac muscle are not as prevalent. Therefore, the first hypothesis

High fat diets (HFD) are known to cause hepatic non-alcoholic steatosis in rats in as few as four weeks. Accumulation of triglycerides in liver and skeletal muscle is associated with insulin resistance and obesity. However, studies of fat accumulation in cardiac muscle are not as prevalent. Therefore, the first hypothesis of this study was that HFD would lead to hepatic steatosis as well as lipid accumulation in pectoralis and cardiac muscles, tissues responsible for the majority of postprandial glucose disposal. Prior studies also indicated that HFD leads to increased inflammation and oxidative stress within the vasculature resulting in impaired endothelium-dependent vasodilation, however biomarkers of immune system reactivity were not assessed. Therefore, the second aim of this study was to explore additional pathways of immune system reactivity and stress (natural antibodies; heat shock protein 60 (HSP60)) in rats fed either a control (chow) or high fat (HFD) diet. HSP60 has also recently been recognized as an early marker of vascular dysfunction in humans. The hypothesis was that immune system reactivity and early vascular dysfunction would be heightened in rats fed a HFD compared to chow-fed controls. Young male Sprague-Dawley rats (140-160g) were maintained on a chow diet (5% fat, 57.33% carbohydrate, 3.4kcal/g) or HFD (60% fat, 20% carbohydrate, 5.24 kcal/g) for 6 weeks. HFD rats developed hepatic steatosis with significantly elevated liver triglyceride concentrations compared to chow-fed controls (20.73±2.09 vs.9.75±0.52 mg triglycerides/g tissue, respectively; p=0.001). While lipid accumulation appeared to be evident in the pectoralis muscle from HFD rats, triglyceride concentrations were not significantly different from controls. Likewise, there was no evidence of lipid infiltration in cardiac muscles of HFD rats. Lipid accumulation in the liver of overweight HFD rats may contribute to the observed insulin resistance in these animals. Contrary to the second hypothesis, there were no significant differences in plasma HSP60 expression between HFD and chow rats (p>0.05). Likewise, hemagglutination and hemolysis responses were similar between HFD and chow-fed rats (p>0.05). These findings suggest that immune system responses may not be affected by 6 weeks of high fat intake and that HSP60 is not an early marker of vascular dysfunction in this rodent model.
ContributorsLiss, Tyler Jessee (Author) / Sweazea, Karen (Thesis director) / Shaibi, Gabriel (Committee member) / Johnston, Carol (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2013-05
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Description
Incentive salience is a motivational-cognitive process that can transform an otherwise neutral stimulus into something that is wanted. The prolonged use of nicotine appears to enhance incentive salience; it has been suggested that the nicotinic enhancement of incentive salience contributes to the potential of relapse in individuals with tobacco addiction.

Incentive salience is a motivational-cognitive process that can transform an otherwise neutral stimulus into something that is wanted. The prolonged use of nicotine appears to enhance incentive salience; it has been suggested that the nicotinic enhancement of incentive salience contributes to the potential of relapse in individuals with tobacco addiction. In order to determine whether (a) nicotinic enhancement of incentive salience for non-nicotinic stimuli occurs when rats self-administer nicotine and (b) a history of nicotine use facilitates such enhancement, rats were trained in a morning self-administration paradigm (SA), in combination with an afternoon 4-CS Pavlovian conditioned approach task (PCA) for 24 days. SA was followed by extinction and cue reinstatement. Nicotine SA enhanced incentive salience in the PCA. Upon extinction, incentive salience quickly declined to saline levels, indicating that the nicotinic enhancement of incentive salience is transient. Experimenter-administered nicotine enhanced incentive salience similarly regardless of nicotine history, suggesting that a previous history of nicotine use does sensitize the nicotinic enhancement of incentive salience. Taken together, these results suggest that nicotine must be onboard for the expression of nicotinic enhancement of incentive salience. This suggests that the role of incentive salience in the development and relapse of tobacco addiction may need to be revisited.
ContributorsOverby, Paula F. (Author) / Sanabria, Federico (Thesis director) / Gipson-Reichardt, Cassandra (Committee member) / Beckmann, Joshua (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05