Matching Items (12)
Description
Globally, addiction to stimulants such as methamphetamine (METH) remains a significant public health problem. Despite decades of research, no approved anti-relapse medications for METH or any illicit stimulant exist, and current treatment approaches suffer from high relapse rates. Recently, synthetic cathinones have also emerged as popular abused stimulants, leading to numerous incidences of toxicity and death. However, contrary to traditional illicit stimulants, very little is known about their addiction potential. Given the high relapse rates and lack of approved medications for METH addiction, chapters 2 and 3 of this dissertation assessed three different glutamate receptor ligands as potential anti-relapse medications following METH intravenous self-administration (IVSA) in rats. In chapters 4 through 7, using both IVSA and intracranial self-stimulation (ICSS) procedures, experiments assessed abuse liability of the popular synthetic cathinones 3,4-Methylenedioxypyrovalerone (MDPV) , methylone, α-pyrrolidinovalerophenone (α-PVP) and 4-methylethylcathinone (4-MEC). Results from these seminal studies suggest that these drugs possess similar abuse potential to traditional illicit stimulants such as METH, cocaine, and 3,4-methylenedioxymethamphetamine (MDMA). Finally, studies outlined in chapter 8 assessed the potential neurotoxic or adverse cognitive effects of METH and MDPV following IVSA procedures for the purpose of identifying potential novel pharmacotherapeutic targets. However, results of these final studies did not reveal neurotoxic or adverse cognitive effects when using similar IVSA procedural parameters that were sufficient for establishing addiction potential, suggesting that these parameters do not allow for sufficient drug intake to produce similar neurotoxicity or cognitive deficits reported in humans. Thus, these models may be inadequate for fully modeling the adverse neural and psychological consequences of stimulant addiction. Together, these studies support the notion for continued research into the abuse liability and toxicity of METH and synthetic cathinones and suggest that refinements to traditional IVSA models are needed for both more effective assessment of potential cognitive and neural deficits induced by these drugs and screening of potentially clinically efficacious pharmacotherapeutics.
ContributorsWatterson, Lucas (Author) / Olive, Michael F (Thesis advisor) / Czyzyk, Traci (Committee member) / Neisewander, Janet (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2014
Description
Females are highly vulnerable to the effects of methamphetamine, and understanding the mechanisms of this is critical to addressing methamphetamine use as a public health issue. Hormones may play a role in methamphetamine sensitivity; thus, the fluctuation of various endogenous peptides during the postpartum experience is of interest. This honors thesis project explored the relation between anxiety-like behavior, as measured by activity in an open field, and conditioned place preference to methamphetamine in female versus male rats. The behavior of postpartum as well as virgin female rats was compared to that of male rats. There was not a significant difference between males and females in conditioned place preference to methamphetamine, yet females showed higher locomotor activity in response to the drug as well as increased anxiety-like behavior in open field testing as compared to males. Further study is vital to comprehending the complex mechanisms of sex differences in methamphetamine addiction.
ContributorsBaker, Allison Nicole (Author) / Olive, M. Foster (Thesis director) / Presson, Clark (Committee member) / Hansen, Whitney (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Polysubstance abuse is far more common than single substance abuse. One of the most widely abused, yet greatly understudied combination of drugs is the simultaneous use of methamphetamine (meth) and alcohol. Because little research has been conducted on the co-abuse of meth and alcohol, it is important to study the behavioral and neural mechanisms underlying the use of both to combat addiction and come closer to finding an effective treatment of this form of drug abuse. This study uses a rodent model to attempt to identify the mechanisms underlying this co-abuse through the stimulation of the medial forebrain bundle (MFB) and thus the activation of the mesocorticolimbic pathway, the brain's pleasure circuit. First, self-stimulation thresholds (the lowest electrical current the rats are willing to respond for) were determined using a process called Discrete Trials Training. This threshold was later used as a baseline measure to reference when the rats were administered the drugs of abuse: meth and alcohol, both alone and in combination. Our overall results did not show any significant effects of combining alcohol and meth relative to the effects of either drug alone, although subject attrition may have resulted in sample sizes that were statistically underpowered. The results of this and future studies will help provide a clearer understanding of the neural mechanisms underlying the polyabuse of meth and alcohol and can potentially lead to more successfully combating and treating this addiction.
ContributorsDrafton, Kaitlyn Marie (Author) / Olive, Foster (Thesis director) / Glenberg, Arthur (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Evidence from the 20th century demonstrated that early life stress (ELS) produces long lasting neuroendocrine and behavioral effects related to an increased vulnerability towards psychiatric illnesses such as major depressive disorder, post-traumatic stress disorder, schizophrenia, and substance use disorder. Substance use disorders (SUDs) are complex neurological and behavioral psychiatric illnesses. The development, maintenance, and relapse of SUDs involve multiple brain systems and are affected by many variables, including socio-economic and genetic factors. Pre-clinical studies demonstrate that ELS affects many of the same systems, such as the reward circuitry and executive function involved with addiction-like behaviors. Previous research has focused on cocaine, ethanol, opiates, and amphetamine, while few studies have investigated ELS and methamphetamine (METH) vulnerability. METH is a highly addictive psychostimulant that when abused, has deleterious effects on the user and society. However, a critical unanswered question remains; how do early life experiences modulate both neural systems and behavior in adulthood? The emerging field of neuroepigenetics provides a potential answer to this question. Methyl CpG binding protein 2 (MeCP2), an epigenetic tag, has emerged as one possible mediator between initial drug use and the transition to addiction. Additionally, there are various neural systems that undergo long lasting epigenetics changes after ELS, such as the response of the hypothalamo-pituitary-adrenal (HPA) axis to stressors. Despite this, little attention has been given to the interactions between ELS, epigenetics, and addiction vulnerability. The studies described herein investigated the effects of ELS on METH self-administration (SA) in adult male rats. Next, we investigated the effects of ELS and METH SA on MeCP2 expression in the nucleus accumbens and dorsal striatum. Additionally, we investigated the effects of virally-mediated knockdown of MeCP2 expression in the nucleus accumbens core on METH SA, motivation to obtain METH under conditions of increasing behavioral demand, and reinstatement of METH-seeking in rats with and without a history of ELS. The results of these studies provide insights into potential epigenetic mechanisms by which ELS can produce an increased vulnerability to addiction in adulthood. Moreover, these studies shed light on possible novel molecular targets for treating addiction in individuals with a history of ELS.
ContributorsLewis, Candace (Author) / Olive, M. Foster (Thesis advisor) / Hammer, Ronald (Committee member) / Neisewander, Janet (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2015
Description
Unmanned aerial vehicles have received increased attention in the last decade due to their versatility, as well as the availability of inexpensive sensors (e.g. GPS, IMU) for their navigation and control. Multirotor vehicles, specifically quadrotors, have formed a fast growing field in robotics, with the range of applications spanning from surveil- lance and reconnaissance to agriculture and large area mapping. Although in most applications single quadrotors are used, there is an increasing interest in architectures controlling multiple quadrotors executing a collaborative task. This thesis introduces a new concept of control involving more than one quadrotors, according to which two quadrotors can be physically coupled in mid-flight. This concept equips the quadro- tors with new capabilities, e.g. increased payload or pursuit and capturing of other quadrotors. A comprehensive simulation of the approach is built to simulate coupled quadrotors. The dynamics and modeling of the coupled system is presented together with a discussion regarding the coupling mechanism, impact modeling and additional considerations that have been investigated. Simulation results are presented for cases of static coupling as well as enemy quadrotor pursuit and capture, together with an analysis of control methodology and gain tuning. Practical implementations are introduced as results show the feasibility of this design.
ContributorsLarsson, Daniel (Author) / Artemiadis, Panagiotis (Thesis advisor) / Marvi, Hamidreza (Committee member) / Berman, Spring (Committee member) / Arizona State University (Publisher)
Created2016
Description
This dissertation explores the historical development and contemporary deployment of discursive practices that constitute the “truth” of addiction, which in turn serve as the bases for interventions into the lives of people who use intoxicants for any number of reasons. A number of interrelated research questions structure this governmentality analysis. First, what is the evolution of the governmental frames developed and deployed to understand, discipline, and recover addiction in the arena of alcohol and illicit drug use in United States? Second, how does twelve-step serve to transform unruly addicts into self-disciplining citizens? Finally, how does The Meth Project (TMP) exemplify and/or diverge from the dominant addiction governmental frames developed during the Temperance and Progressive eras in the United States? My overall goal is to destabilize our ready understanding of addiction and demonstrate that it is as much a tool of social needs as it is a mental illness by demonstrating: 1) the historically contingent nature of our understandings of addiction and addicts; 2) how these historically contingent understandings are actualized as technologies geared toward “recovering” unruly subjects; and 3) how these historically contingent understandings are taken up as “epistemological scripts” used to conceptualize the “true nature” of certain types of drugs and drug users while simultaneously supporting various regimes of discipline and punishment for those determined to remain “unruly subjects.”
ContributorsWalker, Michael F (Author) / Nadesan, Majia H (Thesis advisor) / Provine, Doris M (Thesis advisor) / Cavender, Gray (Committee member) / Brouwer, Daniel C (Committee member) / Arizona State University (Publisher)
Created2016
Description
The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first two weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, opioids, and amphetamine. Methamphetamine (METH) causes great harm to both the individual user and to society; yet, no studies have examined the effects of MS on METH SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) core were also investigated. Long-Evans pups and dams were separated on postnatal days (PND) 2-14 for either 180 (MS180) or 15 min (MS15). Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion) in 15 2-hr daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.
ContributorsLewis, Candace (Author) / Olive, Micheal F (Thesis advisor) / Conrad, Cheryl (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2013
Description
Children removed from methamphetamine laboratories are a severely understudied population despite the widespread deprivation parental methamphetamine abuse has on children, particularly in homes where methamphetamine is produced. Arizona's children are uniquely affected by the use and manufacturing of methamphetamine due to the geographic location and landscape of the state. A sample of 144 children removed from their homes during the seizure of methamphetamine laboratories, as part of the Arizona Drug Endangered Children program between 1999 and 2003, was investigated. Results indicate that younger children were more likely to be reported by Child Protective Services as high or moderate risk of further abuse, test positive for methamphetamine, and have maternal alleged perpetrators of abuse. Older children were more likely to be reported as low risk for further abuse, test negative for methamphetamine, and have paternal alleged perpetrators of abuse. Results also show that children initially placed in foster care were more likely to remain in foster care at the final assessment than to be living with a parent or kin. These findings have implications for individuals working with children removed from methamphetamine laboratories, including Child Protective Services case workers, medical personnel, temporary and permanent child caregivers (i.e., foster care, kin care, adoptive parents, and shelters), and community members (i.e., teachers). Recommendations based on study findings are offered to child and family advocates and interventionists.
ContributorsPennar, Amy LaRae (Author) / Shapiro, Alyson F. (Thesis advisor) / Bradley, Robert H (Committee member) / Krysik, Judy (Committee member) / Arizona State University (Publisher)
Created2011
Description
Serotonin 1B receptors (5-HT1BRs) are a novel target for developing pharmacological therapies to reduce psychostimulant craving. 5-HT1BRs are expressed in the mesolimbic pathway projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), which is involved in reward and motivation. 5-HT1BR agonists modulate both cocaine- and methamphetamine-seeking behaviors in rat models of psychostimulant craving. In this dissertation, I tested the central hypothesis that 5-HT1BRs regulate cocaine and methamphetamine stimulant and rewarding effects in mice. I injected mice daily with cocaine for 20 days and then tested them 20 days after their last injection. The results showed that the 5-HT1BR agonist CP94253 attenuated sensitization of cocaine-induced locomotion and cocaine-seeking behavior, measured as a decrease in the ability of a cocaine priming injection to reinstate extinguished cocaine-conditioned place preference (CPP). Subsequent experiments showed that CP94253 given prior to conditioning sessions had no effect on acquisition of methamphetamine-CPP, a measure of drug reward; however, CP94253 given prior to testing attenuated expression of methamphetamine-CPP, a measure of drug seeking. To examine brain regions and cell types involved in CP94253 attenuation of methamphetamine-seeking, I examined changes in the immediate early gene product, Fos, which is a marker of brain activity involving gene transcription changes. Mice expressing methamphetamine-CPP showed elevated Fos expression in the VTA and basolateral amygdala (BlA), and reduced Fos in the central nucleus of the amygdala (CeA). In mice showing CP94253-induced attenuation of methamphetamine-CPP expression, Fos was increased in the VTA, NAc shell and core, and the dorsal medial caudate-putamen. CP94253 also reversed the methamphetamine-conditioned decrease in Fos expression in the CeA and the increase in the BlA. In drug-naïve, non-conditioned control mice, CP94253 only increased Fos in the CeA, suggesting that the increases observed in methamphetamine-conditioned mice were due to conditioning rather than an unconditioned effect of CP94253 on Fos expression. In conclusion, 5-HT1BR stimulation attenuates both cocaine and methamphetamine seeking in mice, and that the latter effect may involve normalizing activity in the amygdala and increasing activity in the mesolimbic pathway. These findings further support the potential efficacy of 5-HT1BR agonists as pharmacological interventions for psychostimulant craving in humans.
ContributorsDer-Ghazarian, Taleen (Author) / Neisewander, Janet (Thesis advisor) / Olive, Foster (Committee member) / Newbern, Jason (Committee member) / Wu, Jie (Committee member) / Arizona State University (Publisher)
Created2018
Description
There has been a vast increase in applications of Unmanned Aerial Vehicles (UAVs) in civilian domains. To operate in the civilian airspace, a UAV must be able to sense and avoid both static and moving obstacles for flight safety. While indoor and low-altitude environments are mainly occupied by static obstacles, risks in space of higher altitude primarily come from moving obstacles such as other aircraft or flying vehicles in the airspace. Therefore, the ability to avoid moving obstacles becomes a necessity
for Unmanned Aerial Vehicles.
Towards enabling a UAV to autonomously sense and avoid moving obstacles, this thesis makes the following contributions. Initially, an image-based reactive motion planner is developed for a quadrotor to avoid a fast approaching obstacle. Furthermore, A Dubin’s curve based geometry method is developed as a global path planner for a fixed-wing UAV to avoid collisions with aircraft. The image-based method is unable to produce an optimal path and the geometry method uses a simplified UAV model. To compensate
these two disadvantages, a series of algorithms built upon the Closed-Loop Rapid Exploratory Random Tree are developed as global path planners to generate collision avoidance paths in real time. The algorithms are validated in Software-In-the-Loop (SITL) and Hardware-In-the-Loop (HIL) simulations using a fixed-wing UAV model and in real flight experiments using quadrotors. It is observed that the algorithm enables a UAV to avoid moving obstacles approaching to it with different directions and speeds.
for Unmanned Aerial Vehicles.
Towards enabling a UAV to autonomously sense and avoid moving obstacles, this thesis makes the following contributions. Initially, an image-based reactive motion planner is developed for a quadrotor to avoid a fast approaching obstacle. Furthermore, A Dubin’s curve based geometry method is developed as a global path planner for a fixed-wing UAV to avoid collisions with aircraft. The image-based method is unable to produce an optimal path and the geometry method uses a simplified UAV model. To compensate
these two disadvantages, a series of algorithms built upon the Closed-Loop Rapid Exploratory Random Tree are developed as global path planners to generate collision avoidance paths in real time. The algorithms are validated in Software-In-the-Loop (SITL) and Hardware-In-the-Loop (HIL) simulations using a fixed-wing UAV model and in real flight experiments using quadrotors. It is observed that the algorithm enables a UAV to avoid moving obstacles approaching to it with different directions and speeds.
ContributorsLin, Yucong (Author) / Saripalli, Srikanth (Thesis advisor) / Scowen, Paul (Committee member) / Fainekos, Georgios (Committee member) / Thangavelautham, Jekanthan (Committee member) / Youngbull, Cody (Committee member) / Arizona State University (Publisher)
Created2015