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- Genre: Academic theses
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
Three experiments used a spatial serial conditioning paradigm to assess the effectiveness of spatially informative conditioned stimuli in eliciting tracking behavior in pigeons. The experimental paradigm consisted of the simultaneous presentation of 2 key lights (CS2 and CTRL), followed by another key light (CS1), followed by food (the unconditioned stimulus or US). CS2 and CTRL were presented in 2 of 3 possible locations, randomly assigned; CS1 was always presented in the same location as CS2. CS2 was designed to signal the spatial, but not the temporal locus of CS1; CS1 signaled the temporal locus of the US. In Experiment 1, differential pecking on CS2 was observed even when CS2 was present throughout the interval between CS1s, but only in a minority of pigeons. A control condition verified that pecking on CS2 was not due to temporal proximity between CS2 and US. Experiment 2 demonstrated the reversibility of spatial conditioning between CS2 and CTRL. Asymptotic performance never involved tracking CTRL more than CS2 for any of 16 pigeons. It is inferred that pigeons learned the spatial association between CS2 and CS1, and that temporal contingency facilitated its expression as tracking behavior. In a third experiment, with pigeons responding to a touchscreen monitor, differential responding to CS2 was observed only when CS2 disambiguated the location of a random CS1. When the presentation location of CS1 was held constant, no differences in responding to CS2 or CTRL were observed.
ContributorsMazur, Gabriela (Author) / Sanabria, Federico (Thesis advisor) / Killeen, Peter R (Committee member) / Robles-Sotelo, Elias (Committee member) / Ho Chen Cheung, Timothy (Committee member) / Arizona State University (Publisher)
Created2011
Description
The capability of cocaine-associated stimuli in eliciting craving in human addicts, even after extended periods of abstinence, is modeled in animals using cue reinstatement of extinguished cocaine-seeking behavior. This study aimed to examine brain activation in response to cocaine cues in this model apart from activation produced by test novelty using a novel cue control. Rats trained to self-administer cocaine paired with either an oscillating light or tone cue underwent daily extinction training and were then tested for reinstatement of extinguished cocaine-seeking behavior elicited by response-contingent presentations of either their assigned cocaine-paired cue or the alternate, novel cue. Additional controls received saline infusions and cue presentations yoked to a cocaine-trained rat. Brains were harvested for Fos immunohistochemistry immediately after the 90-min reinstatement test. Surprisingly, conditioned and novel cues both reinstated responding to a similar degree; however magnitude of reinstatement did vary by cue modality with the greatest reinstatement to the light cues. In most brain regions, Fos expression was enhanced in rats with a history of cocaine training regardless of cue type with the exception of the Cg1 region of the anterior cingulate cortex, which was sensitive to test cue modality. Also Fos expression within the dorsomedial caudate-putamen was correlated with responding in the novel, but not conditioned, cue groups. In subsequent experiments, we observed a similar pattern of reinstatement in rats trained and tested for sucrose-seeking behavior, whereas rats trained and tested with the cues only reinstated to a novel light and tone, but not a familiar cue. The results suggest that novel cues reinstate responding to a similar extent as conditioned cues regardless of whether animals have a history of operant-delivered drug or a natural reinforcer. Furthermore, similar brain circuits as those involved in cocaine-seeking behavior are activated by novel cues, suggesting converging processes exist to drive conditioned and novel reinforcement seeking.
ContributorsBastle, Ryan (Author) / Neisewander, Janet L (Thesis advisor) / Sanabria, Federico (Committee member) / Olive, Michael F (Committee member) / Arizona State University (Publisher)
Created2012
Description
Social influences are important determinants of drug initiation in humans, particularly during adolescence and early adulthood. My dissertation tested three hypotheses: 1) conditioned and unconditioned nicotine and social rewards elicit unique patterns of neural signaling in the corticolimbic neurocircuitry when presented in combination versus individually; 2) play behavior is not necessary for expression of social reward; and 3) social context enhances nicotine self-administration. To test the first hypothesis, Fos protein was measured in response to social and nicotine reward stimuli given alone or in combination and in response to environmental cues associated with the rewards in a conditioned place preference (CPP) test. Social-conditioned environmental stimuli attenuated Fos expression in the nucleus accumbens core. A social partner elevated Fos expression in the caudate-putamen, medial and central amygdala, and both nucleus accumbens subregions. Nicotine decreased Fos expression in the cingulate cortex, caudate-putamen, and the nucleus accumbens core. Both stimuli combined elevated Fos expression in the basolateral amygdala and ventral tegmental area, suggesting possible overlap in processing both rewards in these regions. I tested the second hypothesis with an apparatus containing compartments separated by a wire mesh barrier that allowed limited physical contact with a rat or object. While 2 pairings with a partner rat (full physical contact) produced robust CPP, additional pairings were needed for CPP with a partner behind a barrier or physical contact with an object (i.e., tennis ball). The results demonstrate that physical contact with a partner rat is not necessary to establish social-reward CPP. I tested the third hypothesis with duplex operant conditioning chambers separated either by a solid or a wire mesh barrier to allow for social interaction during self-administration sessions. Nicotine (0.015 and 0.03 mg/kg, IV) and saline self-administration were assessed in male and female young-adult rats either in the social context or isolation. Initially, a social context facilitated nicotine intake at the low dose in male rats, but suppressed intake in later sessions more strongly in female rats, suggesting that social factors exert strong sex-dependent influences on self-administration. These novel findings highlight the importance of social influences on several nicotine-related behavioral paradigms and associated neurocircuitry.
ContributorsPeartree, Natalie (Author) / Neisewander, Janet L (Thesis advisor) / Conrad, Cheryl D. (Committee member) / Nikulina, Ella M (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2015
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 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
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 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
Description
Chronic stress results in functional and structural changes to the hippocampus. Decades of research has led to insights into the mechanisms underlying the chronic stress-induced deficits in hippocampal-mediated cognition and reduction of dendritic complexity of hippocampal neurons. Recently, a considerable focus of chronic stress research has investigated the mechanisms behind the improvements in hippocampal mediated cognition when chronic stress ends and a post-stress rest period is given. Consequently, the goal of this dissertation is to uncover the mechanisms that allow for spatial ability to improve in the aftermath of chronic stress. In chapter 2, the protein brain derived neurotrophic factor (BDNF) was investigated as a mechanism that allows for spatial ability to show improvements following the end of chronic stress. It was found that decreasing the expression of BDNF in the hippocampus prevented spatial memory improvements following a post-stress rest period. Chapter 3 was performed to determine whether hippocampal CA3 apical dendritic complexity requires BDNF to show improvements following a post-stress rest period, and whether a receptor for BDNF, TrkB, mediates the improvements of spatial ability and dendritic complexity in a temporal manner, i.e. during the rest period only. These experiments showed that decreased hippocampal BDNF expression prevented improvements in dendritic complexity, and administration of a TrkB antagonist during the rest period also prevented the improvements in spatial ability and dendritic complexity. In chapter 4, the role of the GABAergic system on spatial ability following chronic stress and a post-stress rest period was investigated. Following chronic stress, it was found that male rats showed impairments on the acquisition phase of the RAWM and this correlated with limbic glutamic acid decarboxylase, a marker for GABA. In chapter 5, a transgenic mouse that expresses a permanent marker on all GABAergic interneurons was used to assess the effects of chronic stress and a post-stress rest period on hippocampal GABAergic neurons. While no changes were found on the total number of GABAergic interneurons, specific subtypes of GABAergic interneurons were affected by stressor manipulations. Collectively, these studies reveal some mechanisms behind the plasticity seen in the hippocampus in response to a post-stress rest period.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Newbern, Jason M. (Committee member) / Orchinik, Miles (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2018
Description
The attractiveness of a reward depends in part on the delay to its receipt, with more distant rewards generally being valued less than more proximate ones. The rate at which people discount the value of delayed rewards has been associated with a variety of clinically and socially relevant human behaviors. Thus, the accurate measurement of delay discounting rates is crucial to the study of mechanisms underlying behaviors such as risky sex, addiction, and gambling. In delay discounting tasks, participants make choices between two alternatives: one small amount of money delivered immediately versus a large amount of money delivered after a delay. After many choices, the experimental task will converge on an indifference point: the value of the delayed reward that approximates the value of the immediate one. It has been shown that these indifference points are systematically biased by the direction in which one of the alternatives adjusts. This bias is termed a sequencing effect.
The present research proposed a reference-dependent model of choice drawn from Prospect Theory to account for the presence of sequencing effects in a delay discounting task. Sensitivity to reference frames and sequencing effects were measured in two computer tasks. Bayesian and frequentist analyses indicated that the reference-dependent model of choice cannot account for sequencing effects. Thus, an alternative, perceptual account of sequencing effects that draws on a Bayesian framework of magnitude estimation is proposed and furnished with some preliminary evidence. Implications for future research in the measurement of delay discounting and sensitivity to reference frames are discussed.
The present research proposed a reference-dependent model of choice drawn from Prospect Theory to account for the presence of sequencing effects in a delay discounting task. Sensitivity to reference frames and sequencing effects were measured in two computer tasks. Bayesian and frequentist analyses indicated that the reference-dependent model of choice cannot account for sequencing effects. Thus, an alternative, perceptual account of sequencing effects that draws on a Bayesian framework of magnitude estimation is proposed and furnished with some preliminary evidence. Implications for future research in the measurement of delay discounting and sensitivity to reference frames are discussed.
ContributorsBecker, Ryan J (Author) / Robles, Elías (Thesis advisor) / Sanabria, Federico (Committee member) / Hall, Deborah L. (Committee member) / Arizona State University (Publisher)
Created2018
Description
The goal of the present study was to investigate whether a rest period following the end of chronic stress would impact fear extinction. Past research has indicated that chronic stress leads to impairments in the learning and recall of fear conditioning extinction. Moreover, the effects of chronic stress can return to levels similar to controls when a post-stress “rest” period (i.e., undisturbed except for normal husbandry) is given prior to testing. Male rats underwent chronic restraint stress for 6hr/day/21days (STR-IMM). Some rats, underwent a post-stress rest period for 6- or 3-weeks after the end of stress (STR-R6, STR-R3). Control (CON) rats were unrestrained for the duration of the experiment. In Experiment 1, following the stress or rest manipulation, all rats were acclimated to conditioning and extinction contexts, fear conditioned with 3 tone-foot shock pairings, and then had two days of extinction training. All groups froze similarly to the tone across all training sessions. However, STR-R6/R3 froze less in the non-shock context than did STR-IMM or CON. During extinction training, STR-IMM showed high levels of freezing to the non-shock context, leading to a concern they may be generalizing across contexts. Consequently, a follow-up experiment tested for context generalization. In Experiment 2, STR-IMM rats underwent a generalization test in an environment that was either different or the same as the conditioning environment, using STR-R6 as a comparison. STR-IMM and STR-R6 showed similar relative levels of freezing to tone and context, regardless of their conditioning environment to reveal that STR-IMM did not generalize and instead, maybe expressing hypervigilance. Thus, the present study demonstrated the novel finding that a rest period from chronic stress can lead to reduced fear responsiveness in a non-shock environment.
ContributorsJudd, Jessica M (Author) / Conrad, Cheryl D. (Thesis advisor) / Sanabria, Federico (Committee member) / Smith, Brian (Committee member) / Arizona State University (Publisher)
Created2018
Description
Temporal bisection is a common procedure for the study of interval timing in humans and non-human animals, in which participants are trained to discriminate between a “short” and a “long” interval of time. Following stable and accurate discrimination, unreinforced probe intervals between the two values are tested. In temporal bisection studies, intermediate non-reinforced probe intervals are typically arithmetically- or geometrically- spaced, yielding point of subjective equality at the arithmetic and geometric mean of the trained anchor intervals. Brown et al. (2005) suggest that judgement of the length of an interval, even when not reinforced, is influenced by its subjective length in comparison to that of other intervals. This hypothesis predicts that skewing the distribution of probe intervals shifts the psychophysical function relating interval length to the probability of reporting that interval as “long.” Data from the present temporal bisection study, using rats, suggest that there may be a within-session shift in temporal bisection responding which accounts for observed shifts in the psychophysical functions, and that this may also influence how rats categorize ambiguous intervals.
ContributorsGupta, Tanya A. (Author) / Sanabria, Federico (Thesis advisor) / Wynne, Clive (Committee member) / McBeath, Michael (Committee member) / Arizona State University (Publisher)
Created2019