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5-HT2A receptor (R) antagonists and 5-HT2CR agonists attenuate reinstatement of cocaine-seeking behavior (i.e., incentive motivation). 5-HT2Rs are distributed throughout the brain, primarily in regions involved in reward circuitry, including the prefrontal cortex (PFC), caudate putamen (CPu), and basolateral (BlA) and central (CeA) amygdala. Using animal models, we tested our hypotheses

5-HT2A receptor (R) antagonists and 5-HT2CR agonists attenuate reinstatement of cocaine-seeking behavior (i.e., incentive motivation). 5-HT2Rs are distributed throughout the brain, primarily in regions involved in reward circuitry, including the prefrontal cortex (PFC), caudate putamen (CPu), and basolateral (BlA) and central (CeA) amygdala. Using animal models, we tested our hypotheses that 5-HT2ARs in the medial (m) PFC mediate the incentive motivational effects of cocaine and cocaine-paired cues; 5-HT2ARs and 5-HT2CRs interact to attenuate cocaine hyperlocomotion and functional neuronal activation (i.e, Fos protein); and 5-HT2CRs in the BlA mediate the incentive motivational effects of cocaine-paired cues and anxiety-like behavior, while 5-HT2CRs in the CeA mediate the incentive motivational effects of cocaine. In chapter 2, we infused M100907, a selective 5-HT2AR antagonist, directly into the mPFC and examined its effects on reinstatement of cocaine-seeking behavior. We found that M100907 in the mPFC dose- dependently attenuated cue-primed reinstatement, without affecting cocaine-primed reinstatement, cue-primed reinstatement of sucrose-seeking behavior, or locomotor activity. In chapter 3, we used subthreshold doses of M100907 and MK212, a 5-HT2CR agonist, to investigate whether these compounds interact to attenuate cocaine hyperlocomotion and Fos protein expression. Only the drug combination attenuated cocaine hyperlocomotion and cocaine-induced Fos expression in the CPu, but had no effect on spontaneous locomotion. Finally, in chapter 4 we investigated the effects of a 5- HT2CR agonist in the BlA and CeA on cocaine-seeking behavior and anxiety-like behavior. We found that CP809101, a selective 5-HT2CR agonist, infused into the BlA increased anxiety-like behavior on the elevated plus maze (EPM), but failed to alter cocaine-seeking behavior. CP809101 infused into the CeA attenuated cocaine-primed reinstatement and this effect was blocked by co-administration of a 5-HT2CR antagonist. Together, these results suggest that 5-HT2ARs in the mPFC are involved in cue-primed reinstatement, 5-HT2A and 5-HT2CRs may interact in the nigrostriatal pathway to attenuate cocaine hyperlocomotion and Fos expression, and 5-HT2CRs are involved in anxiety-like behavior in the BlA and cocaine-primed reinstatement in the CeA. Our findings add to the literature on the localization of 5-HT2AR antagonist and 5-HT2CR agonist effects, and suggest a potential treatment mechanism via concurrent 5-HT2AR antagonism and 5-HT2CR agonism.
ContributorsPockros, Lara Ann (Author) / Neisewander, Janet L (Thesis advisor) / Olive, Michael F (Committee member) / Conrad, Cheryl D. (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Patients with schizophrenia have deficits in sensorimotor gating, the ability to gate out irrelevant stimuli in order to attend to relevant stimuli. Prepulse inhibition (PPI) of the startle response is a reliable and valid model of sensorimotor gating across species. Repeated D2-like agonist treatment alleviates prior PPI deficits in rats,

Patients with schizophrenia have deficits in sensorimotor gating, the ability to gate out irrelevant stimuli in order to attend to relevant stimuli. Prepulse inhibition (PPI) of the startle response is a reliable and valid model of sensorimotor gating across species. Repeated D2-like agonist treatment alleviates prior PPI deficits in rats, termed a PPI recovery, and is observable 28 days after treatment. The aim of the current project is to illuminate the underlying mechanism for this persistent change of behavior and determine the clinical relevance of repeated D2-like agonist treatment. Our results revealed a significant increase in Delta FosB, a transcription factor, in the nucleus accumbens (NAc) 10 days after repeated D2-like agonist treatment. Additionally, we investigated if Delta FosB was necessary for long-lasting PPI recovery and discovered a bilateral infusion of dominant-negative Delta JunD prevented PPI recovery after repeated D2-like agonist treatment. To further develop the underlying mechanism of PPI recovery, we observed that dominant negative mutant cyclic adenosine monophosphate (cAMP) response biding element protein (CREB) prevented repeated D2-like agonist-induced Delta FosB expression in the NAc. We then compared our previous behavioral and intracellular findings to the results of repeated aripiprazole, a novel D2-like partial agonist antipsychotic, to determine if repeated D2-like receptor agonist action is a clinically relevant pharmacological approach. As compared to previous PPI recovery and Delta FosB expression after repeated D2-like agonist treatment, we found similar PPI recovery and Delta FosB expression after repeated aripiprazole treatment in rats. We can conclude that repeated D2-like agonist treatment produces persistent PPI recovery through CREB phosphorylation and Delta FosB, which is necessary for PPI recovery. Furthermore, this pharmacological approach produces behavioral and intracellular changes similar to an effective novel antipsychotic. These findings suggest the underlying intracellular mechanism for sustained PPI recovery is clinically relevant and may be a potential target of therapeutic intervention to alleviate sensorimotor gating deficits, which are associated with cognitive symptoms of schizophrenia.
ContributorsMaple, Amanda (Author) / Hammer, Ronald P. (Thesis advisor) / Olive, Michael F (Committee member) / Gallitano, Amelia L (Committee member) / Conrad, Cheryl D. (Committee member) / Nikulina, Ella M (Committee member) / Arizona State University (Publisher)
Created2013
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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

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
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Description
Many individual-level behavioral interventions improve health and well-being. However, most interventions exhibit considerable heterogeneity in response. Put differently, what might be effective on average might not be effective for specific individuals. From an individual’s perspective, many healthy behaviors exist that seem to have a positive impact. However, few existing tools

Many individual-level behavioral interventions improve health and well-being. However, most interventions exhibit considerable heterogeneity in response. Put differently, what might be effective on average might not be effective for specific individuals. From an individual’s perspective, many healthy behaviors exist that seem to have a positive impact. However, few existing tools support people in identifying interventions that work for them, personally.

One approach to support such personalization is via self-experimentation using single-case designs. ‘Hack Your Health’ is a tool that guides individuals through an 18-day self-experiment to test if an intervention they choose (e.g., meditation, gratitude journaling) improves their own psychological well-being (e.g., stress, happiness), whether it fits in their routine, and whether they enjoy it.

The purpose of this work was to conduct a formative evaluation of Hack Your Health to examine user burden, adherence, and to evaluate its usefulness in supporting decision-making about a health intervention. A mixed-methods approach was used, and two versions of the tool were tested via two waves of participants (Wave 1, N=20; Wave 2, N=8). Participants completed their self-experiments and provided feedback via follow-up surveys (n=26) and interviews (n=20).

Findings indicated that the tool had high usability and low burden overall. Average survey completion rate was 91%, and compliance to protocol was 72%. Overall, participants found the experience useful to test if their chosen intervention helped them. However, there were discrepancies between participants’ intuition about intervention effect and results from analyses. Participants often relied on intuition/lived experience over results for decision-making. This suggested that the usefulness of Hack Your Health in its current form might be through the structure, accountability, and means for self-reflection it provided rather than the specific experimental design/results. Additionally, situations where performing interventions within a rigorous/restrictive experimental set-up may not be appropriate (e.g., when goal is to assess intervention enjoyment) were uncovered. Plausible design implications include: longer experimental and phase durations, accounting for non-compliance, missingness, and proximal/acute effects, and exploring strategies to complement quantitative data with participants’ lived experiences with interventions to effectively support decision-making. Future work should explore ways to balance scientific rigor with participants’ needs for such decision-making.
ContributorsPhatak, Sayali Shekhar (Author) / Buman, Matthew P (Thesis advisor) / Hekler, Eric B. (Committee member) / Huberty, Jennifer L (Committee member) / Johnston, Erik W., 1977- (Committee member) / Swan, Pamela D (Committee member) / Arizona State University (Publisher)
Created2019
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Description
The purpose of this study was to examine the feasibility and preliminary efficacy of a theory-driven and a atheoretical reminder point-of-choice (PoC) prompt interventions on reducing workplace sedentary behavior in office workers with self-reported low usage (<4 hours per day) of their sit-stand workstations in the standing position. The design

The purpose of this study was to examine the feasibility and preliminary efficacy of a theory-driven and a atheoretical reminder point-of-choice (PoC) prompt interventions on reducing workplace sedentary behavior in office workers with self-reported low usage (<4 hours per day) of their sit-stand workstations in the standing position. The design of this study was a cross-over trial including randomization into either the theory-driven or atheoertical reminder condition, after completion of a no prompt control condition. Participants (N=19) included full-time, primarily female, Caucasian, middle-aged office workers. The primary aim of this study was to assess the feasibility of these two PoC prompt conditions on reducing sedentary behaviors through the use of a Therapy Evaluation Questionnaire. The secondary aim of this study was to assess the preliminary efficacy of the two PoC prompt conditions on reducing sedentary behaviors relative to no-prompt control using the activPAL micro device. For the primary aim, descriptive means adjusted for ordering effect were computed. For the secondary aim, mixed-effects regression models were used to cluster for observations within-persons and were adjusted for age, gender, race, job-type, and ordering effects. During the no-prompt control, participants spent 267.90 ± 68.01 sitting and 170.20 ± 69.34 min/8hr workday standing. The reminder PoC prompt condition significantly increased sanding time (b[se] = 24.52 [11.09], p=0.034) while the theory-driven PoC condition significantly decreased time spent in long sitting bouts b[se] = -34.86 [16.20], p=0.036), both relative to no prompt control. No statistically significant reductions in sitting time were seen in either PoC prompt condition. Furthermore, no statistically significant differences between the two PoC prompt conditions were observed. This study provides feasibility insight in addition to objective measures of sedentary behaviors regarding the use of PoC prompt interventions in the workplace.
ContributorsLarouche, Miranda (Author) / Buman, Matthew P (Thesis advisor) / Ainsworth, Barbara E (Thesis advisor) / Huberty, Jennifer L (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Division of labor is a hallmark for social insects and is closely related to honey bee morphology and physiology. Vitellogenin (Vg), a precursor protein in insect egg yolk, has several known functions apart from serving as a nutrient source for developing eggs. Vg is a component in the royal jelly

Division of labor is a hallmark for social insects and is closely related to honey bee morphology and physiology. Vitellogenin (Vg), a precursor protein in insect egg yolk, has several known functions apart from serving as a nutrient source for developing eggs. Vg is a component in the royal jelly produced in the hypopharyngeal glands (HPG) of worker bees which is used to feed both the developing brood and the queen. The HPG is closely associated with divisions of labor as the peak in its development corresponds with the nursing behavior. Independent of the connection between Vg and the HPG, Vg has been seen to play a fundamental role in divisions of labor by affecting worker gustatory responses, age of onset of foraging, and foraging preferences. Similar to Vg, the number of ovarioles in worker ovaries is also associated with division of labor as bees with more ovarioles tend to finish tasks in the hive and become foragers faster. This experiment aims to connect HPGs, ovaries, and Vg by proposing a link between them in the form of ecdysone (20E). 20E is a hormone produced by the ovaries and is linked to ovary development and Vg by tyramine titers. By treating young emerged bees with ecdysone and measuring HPG and ovary development over a trial period, this experiment seeks to determine whether 20E affects division of labor through Vg. We found that though the stress of injection caused a significant decrease in development of both the ovaries and HPG, there was no discernable effect of 20E on either of these organs.
ContributorsChin, Elijah Seth (Author) / Wang, Ying (Thesis director) / Page, Robert (Committee member) / Cook, Chelsea (Committee member) / School of Molecular Sciences (Contributor) / W. P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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This study aimed to identify the emotional/affective sources of discrepancies between physical activity behavior and a widely used self-perception measure of physical activity motivation. Overweight women (body mass index [BMI] ≥ 25 kg/m2, 18-64 years of age; N=37) were recruited from Arizona State University community through flyers and online newsletters.

This study aimed to identify the emotional/affective sources of discrepancies between physical activity behavior and a widely used self-perception measure of physical activity motivation. Overweight women (body mass index [BMI] ≥ 25 kg/m2, 18-64 years of age; N=37) were recruited from Arizona State University community through flyers and online newsletters. Participants wore a SenseWear accelerometer for 6 nights and 7 days and followed their normal patterns of daily living. Participants then completed a single lab visit and verbally responded to questions from the Behavorial Regulation Exercise Questionnaire (BREQ-2) while being video and audio recorded. Captured emotional responses were evaluated with facial recognition software (Noldus FaceReader). Discrepancies between BREQ-2 responses and physical activity behavior were associated with happiness and sadness emotional responses extracted from the facial recognition software using regression-based analyses. Results indicated an association between monitored physical activities and captured emotional response - specifically sadness - and that as intensity in physical activity increases, motivation increases. Associations between happiness/sadness and physical activity were not observed for all intensities of physical activity. A marginally significant association was observed for amotivation and sedentary, light-intensity physical activity, and moderate-vigorous physical activity in the sample. This study demonstrates a proof-of-concept for the integration of an empirical evaluation of happiness and sadness emotional states into the relationship between physical activity motivation and behavior.
ContributorsBryant, Sarah (Author) / Buman, Matthew P (Thesis advisor) / Chisum, Jack W (Committee member) / Hekler, Eric (Committee member) / Arizona State University (Publisher)
Created2016
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Description
The 24-hour day is spent engaging in activities that include light-physical activity (LPA), moderate-vigorous physical activity (MVPA), sedentary time (i.e., sitting/lying/reclining posture with energy expenditure <1.5 METs, while awake), and sleep. These behaviors are mutually exclusive and time spent in one behavior affects the time spent in another. The time

The 24-hour day is spent engaging in activities that include light-physical activity (LPA), moderate-vigorous physical activity (MVPA), sedentary time (i.e., sitting/lying/reclining posture with energy expenditure <1.5 METs, while awake), and sleep. These behaviors are mutually exclusive and time spent in one behavior affects the time spent in another. The time among these 24-hour behaviors is also associated with cardiometabolic health outcomes, including adiposity. Assessing specific behavioral contexts and their relationship within the 24-hour day is underdeveloped, this includes recreational sedentary screen time (rSST). rSST is sedentary time with televisions, computers, smartphones, tablets, inactive video games, and its relationship with other 24-hour behaviors is underdeveloped. This dissertation works evaluates the relationship between rSST and 24-hour behaviors, and adiposity in adults. The first study reviewed the existing observational and experimental evidence for rSST and its relationship with 24-hour behaviors by conducting a scoping review. From the 75 experimental and observational studies included, the evidence supported an overall positive association between rSST and non-screen sedentary behavior, an overall negative association between rSST with physical activity, and overall positive and negative associations between rSST with various sleep variables. The second study assessed the daily associations between rSST and 24-hour behaviors and how associations are influenced by age, sex, chronotype, and week- or weekend days. The findings include significant negative associations at between- and within-person levels for rSST with non-screen sedentary time, standing, LPA, MVPA, and sleep that were differentially influenced by age, chronotype, and week- or weekend day. The third study examined reallocating time between rSST and 24-hour behaviors and the associations with adiposity (i.e., body mass index, body fat percentage, and waist circumference). The results showed significant associations of replacing non-screen sedentary time with MVPA for both body fat percentage and waist circumference; and no significant associations between rSST and 24-hour behaviors for body mass index. Overall, this dissertation work provides important insights into the relationships between rSST and 24-hour behaviors and their relation to adiposity. These findings can be used to inform future intervention development targeting multiple behavior changes and improving health outcomes.
ContributorsHasanaj, Kristina (Author) / Buman, Matthew P (Thesis advisor) / Petrov, Megan E (Thesis advisor) / Sears, Dorothy D (Committee member) / Yu, Fang (Committee member) / Keadle, Sarah K (Committee member) / Arizona State University (Publisher)
Created2023
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Honeybees require the use of their antennae to perceive different scents and pheromones, communicate with other members of the colony, and even detect wind vibrations, sound waves, and carbon dioxide levels. Limiting and/or removing this sense makes bees much less effective at acquiring information. However, how antennal movements might be

Honeybees require the use of their antennae to perceive different scents and pheromones, communicate with other members of the colony, and even detect wind vibrations, sound waves, and carbon dioxide levels. Limiting and/or removing this sense makes bees much less effective at acquiring information. However, how antennal movements might be important for olfaction has not been studied in detail. The focus of this work was to evaluate how restriction of antennae movements might affect a bee’s ability to detect and perceive odors. Bees were made to learn a certain odor and were then split up into a control group, a treatment group that had their antennae fixed with eicosane, and a sham treatment group that had a dot of eicosane on their heads in such a way that it would not affect antennae movements but still add the same amount of weight. Following a period of acclimation, the bees were tested with the conditioned odor, one that was perceptually similar to it, and to a dissimilar odor. Using proboscis-extension duration and latency as response measures, it became clear that both antenna fixation and sham treatments affected the conditioned behavior. However, these treatment effects did not reach statistical significance. Briefly, both fixation of antennae as well as the sham treatment reduced the discriminability of the conditioned and similar odors. Although more data can be collected to more fully evaluate the significance of the treatments, the behavior of the sham group could indicate that mechanoreceptive hairs on the head play an important role in olfaction. It is also possible that there are other factors at play, possibly induced by the fixed bees’ increased stress levels.
ContributorsHozan, Alvin Robert (Author) / Smith, Brian H (Thesis advisor) / Lei, Hong (Committee member) / Cook, Chelsea (Committee member) / Arizona State University (Publisher)
Created2021
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Greater than 11% of the total population of Americans age 12 and older were illicit drug users with close to 1 million suffering from cocaine use disorder in 2017 alone (SAMHSA, 2017), yet there are no effective pharmacological treatments for this disorder. Previous research from the Neisewander Laboratory in male

Greater than 11% of the total population of Americans age 12 and older were illicit drug users with close to 1 million suffering from cocaine use disorder in 2017 alone (SAMHSA, 2017), yet there are no effective pharmacological treatments for this disorder. Previous research from the Neisewander Laboratory in male rats found that administration of a 5-HT1BR agonist facilitates cocaine intake when given prior to a daily self-administration session, while inhibiting cocaine intake and attenuating drug-seeking behavior following 21 days of protracted abstinence, yet it is not known whether such effects are observed in female rats. Women face unique challenges in all phases of the drug addiction cycle. With respect to active drug-taking (i.e., the maintenance phase), women tend to increase their rate of consumption more rapidly than men, and female rats acquire cocaine self-administration faster than males. In part, this is due to ovarian hormone influences on the reinforcing properties of cocaine, where peak levels of endogenous estrogen hormones correspond to an increase in cocaine intake. In this study, we investigated the effects of CP94253, a selective 5HT1BR agonist, on cocaine intake across all phases of the estrous cycle in female rats. The rats were trained to self-administer cocaine (0.75 mg/kg, IV) on a fixed ratio (FR) 5 schedule of reinforcement and daily vaginal smears were taken after each session to monitor the estrous cycle. Rats were pretreated with CP 94,253 (5.6 mg/kg, IP) or vehicle prior to separate tests during each estrous cycle phase and were then either given 1-h access to 0.75 mg/kg cocaine followed by 1-h access to 0.375 mg/kg cocaine or 1-h access to 0.1875 mg/kg cocaine followed by 1-h access to 0.075 mg/kg cocaine. Similar to males, CP 94,253 decreased cocaine intake in females at intermediate doses, however, the estrous cycle phase did not alter this effect.
ContributorsScott, Samantha Nicola (Author) / Neisewander, Janet L (Thesis advisor) / Olive, Michael F (Committee member) / Orchinik, Miles (Committee member) / Arizona State University (Publisher)
Created2019