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- All Subjects: psychology
- All Subjects: Nicotine
- Creators: Sanabria, Federico
- Resource Type: Text
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
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
ContributorsChandler, N. Kayla (Author) / Neisewander, Janet (Thesis director) / Sanabria, Federico (Committee member) / Olive, M. Foster (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05
Description
Stress activates physiological systems within the body to protect oneself against the potential harmful effects of enduring long-term stress. Past studies have shown that structures involved in timing are implicated in a number of psychological disorders and further are sensitive to stress. In this experiment, Sprague Dawley rats are trained to perform a perspective timing task and are then exposed to twice-daily chronic variable stress for 21 days. Behavioral data are collected, followed by post-mortem tissue analysis of the PFC, hippocampus, and striatum. This study aims to examine the morphological changes in key brain regions such as the hippocampus that appear to be involved in interval timing. Additionally, this study aims to confirm that dendritic complexity in the hippocampus produces consistent data using a classic Sholl analysis versus using a virtual image-stacking software, Neurostackr. The results of this study demonstrate that the expected Gaussian graph produced from a classic Sholl analysis was produced from both a long-shaft and short-shaft neuron found in the hippocampus using the virtual technology. These findings verify that a virtual image-stacking software and Sholl analysis will suffice in place of the traditional method of hand traced neurons on a transparent sheet with concentric circles to count bifurcation points. This virtual method ultimately reduces cost, improves timeliness of data collection, and eliminates some of the subjectivity of human error.
ContributorsGarcia, Jasmine Brooke (Author) / Sanabria, Federico (Thesis director) / Gupta, Tanya (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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. 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
Description
The present study examined how systemic low doses of nicotine affect the microstructure of food-reinforced behavior in rats. Rats were given an acute saline or nicotine treatment (0.1-0.6 mg/kg, resting at least 48 h between injections), and a chronic saline or nicotine treatment (0.3 mg/kg for 10 consecutive days). Immediately after treatment, rats were required to press a lever to obtain food, whose availability was unpredictable, but programmed at a constant rate (on average every 80 s). Acute nicotine dose-dependently suppressed behavior prior to the delivery of the first reinforcer, but enhanced food-reinforced behavior afterwards. This effect was primarily observed in the time it took rats to initiate food-seeking behavior, and not in the food-seeking behavior itself. A pre-feeding control procedure suggests that these effects cannot be explained only by changes in appetite. Over the course of chronic nicotine exposure, tolerance developed to the suppressive, but not to the enhancing effects of nicotine on food-seeking behavior. These results suggest that ostensive sensitization effects of nicotine on behavior may instead reflect a tolerance for its suppressive effects on behavior.
ContributorsRomero, Korinna Estela (Author) / Sanabria, Federico (Thesis director) / Gipson-Reichardt, Cassandra (Committee member) / Bevins, Rick (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The rate at which an operant is produced has often functioned as a fundamental measure of the efficacy of a reinforcer. Previous research has shown that operant behavior is typically organized into bouts implying that rate of responding is a composite of bout-initiation rate, within-bout response rate, and mean bout length. However, it is still unclear whether this organization of behavioral responses into bouts is a product of the motivational processes or a property that arises from the location of an organism in space. To test this proximity hypothesis, two-response sequences were intermittently reinforced: either pressing one lever twice (manipulandum proximal to response termination) or pressing each of two levers, located on either side of an operant chamber, once (manipulandum distal to response termination). In Experiment 1, rats were first trained to lever press for food on a VI schedule before being exposed to the alternation paradigm. Experiment 1 consisted of three phases. In Phase 1, food-deprived rats learned the alternation paradigm under a tandem variable time (VT) 150-s fixed-ratio (FR) 1 schedule of reinforcement. Phase 2 and 3 increased the FR requirement from 1 to 3 or 5 and removed food deprivation, respectively, to examine their effect on response-rate components. In Experiment 2, rats switched between trials consisting of pressing a single lever repeatedly or alternating between two levers for reward. Following stable behavior, lever pressing was extinguished in both trial types to the effect of extinction on response-rate components. Overall, behavioral bouts persisted under the alternation paradigm suggesting that they reflect motivational states and not just location. Additionally, bout-initiation rate decreased with increased response effort and decreased deprivation. Taken together, these results provide support for the use of response-bout analysis to evaluate the value of a reinforcer and its sensitivity to pharmacological manipulations.
ContributorsGildea, Matthew (Author) / Sanabria, Federico (Thesis advisor) / Gewirtz, Jonathan (Committee member) / Verpeut, Jessica (Committee member) / Arizona State University (Publisher)
Created2024