Matching Items (12)
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- All Subjects: Behavioral Sciences
- Creators: Neisewander, Janet L
- Creators: Buman, Matthew P
Description
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
Description
Cognitive function declines with normal age and disease states, such as Alzheimer's disease (AD). Loss of ovarian hormones at menopause has been shown to exacerbate age-related memory decline and may be related to the increased risk of AD in women versus men. Some studies show that hormone therapy (HT) can have beneficial effects on cognition in normal aging and AD, but increasing evidence suggests that the most commonly used HT formulation is not ideal. Work in this dissertation used the surgically menopausal rat to evaluate the cognitive effects and mechanisms of progestogens proscribed to women. I also translated these questions to the clinic, evaluating whether history of HT use impacts hippocampal and entorhinal cortex volumes assessed via imaging, and cognition, in menopausal women. Further, this dissertation investigates how sex impacts responsiveness to dietary interventions in a mouse model of AD. Results indicate that the most commonly used progestogen component of HT, medroxyprogesterone acetate (MPA), impairs cognition in the middle-aged and aged surgically menopausal rat. Further, MPA is the sole hormone component of the contraceptive Depo Provera, and my research indicates that MPA administered to young-adult rats leads to long lasting cognitive impairments, evident at middle age. Natural progesterone has been gaining increasing popularity as an alternate option to MPA for HT; however, my findings suggest that progesterone also impairs cognition in the middle-aged and aged surgically menopausal rat, and that the mechanism may be through increased GABAergic activation. This dissertation identified two less commonly used progestogens, norethindrone acetate and levonorgestrel, as potential HTs that could improve cognition in the surgically menopausal rat. Parameters guiding divergent effects on cognition were discovered. In women, prior HT use was associated with larger hippocampal and entorhinal cortex volumes, as well as a modest verbal memory enhancement. Finally, in a model of AD, sex impacts responsiveness to a dietary cognitive intervention, with benefits seen in male, but not female, transgenic mice. These findings have clinical implications, especially since women are at higher risk for AD diagnosis. Together, it is my hope that this information adds to the overarching goal of optimizing cognitive aging in women.
ContributorsBraden, Brittany Blair (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Neisewander, Janet L (Committee member) / Conrad, Cheryl D. (Committee member) / Baxter, Leslie C (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cognitive function is multidimensional and complex, and research indicates that it is impacted by age, lifetime experience, and ovarian hormone milieu. One particular domain of cognitive function that is susceptible to age-related decrements is spatial memory. Cognitive practice can affect spatial memory when aged in both males and females, and in females alone ovarian hormones have been found to alter spatial memory via modulating brain microstructure and function in many of the same brain areas affected by aging. The research in this dissertation has implications that promote an understanding of the effects of cognitive practice on aging memory, why males and females respond differently to cognitive practice, and the parameters and mechanisms underlying estrogen's effects on memory. This body of work suggests that cognitive practice can enhance memory when aged and that estrogen is a probable candidate facilitating the observed differences in the effects of cognitive practice depending on sex. This enhancement in cognitive practice effects via estrogen is supported by data demonstrating that estrogen enhances spatial memory and hippocampal synaptic plasticity. The estrogen-facilitated memory enhancements and alterations in hippocampal synaptic plasticity are at least partially facilitated via enhancements in cholinergic signaling from the basal forebrain. Finally, age, dose, and type of estrogen utilized are important factors to consider when evaluating estrogen's effects on memory and its underlying mechanisms, since age alters the responsiveness to estrogen treatment and the dose of estrogen needed, and small alterations in the molecular structure of estrogen can have a profound impact on estrogen's efficacy on memory. Collectively, this dissertation elucidates many parameters that dictate the outcome, and even the direction, of the effects that cognitive practice and estrogens have on cognition during aging. Indeed, many parameters including the ones described here are important considerations when designing future putative behavioral interventions, behavioral therapies, and hormone therapies. Ideally, the parameters described here will be used to help design the next generation of interventions, therapies, and nootropic agents that will allow individuals to maintain their cognitive capacity when aged, above and beyond what is currently possible, thus enacting lasting improvement in women's health and public health in general.
ContributorsTalboom, Joshua S (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Conrad, Cheryl D. (Committee member) / Neisewander, Janet L (Committee member) / West, Stephen G. (Committee member) / Arizona State University (Publisher)
Created2011
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
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.
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
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 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
Description
Nicotine self-administration is associated with decreased expression of the glial glutamate transporter 1 (GLT-1) and the cystine-glutamate exchange protein xCT in the nucleus accumbens core (NAcore). N-acetylcysteine (NAC), which is an antioxidant, anti-inflammatory, and glutamatergic agent, restores these proteins associated with increased relapse vulnerability. However, the specific molecular mechanisms driving NAC inhibitory effects on cue-induced nicotine reinstatement are unknown. Thus, the present study assessed NAC’s effects on cue-induced nicotine reinstatement are dependent on NAcore GLT-1 expression. Here, rats were treated with NAC in combination with intra-NAcore vivo-morpholinos to examine the role of GLT-1 in NAC-mediated inhibition of cue-induced nicotine seeking. Subchronic NAC treatment attenuated cue-induced nicotine seeking in male rats and an antisense vivo-morpholino (AS) designed to selectively suppress GLT-1 expression in the NAcore blocked this effect. NAC treatment was also associated with an inhibition of pro-inflammatory tumor necrosis factor alpha (TNFα) expression in the NAcore. As well, GLT-1 AS markedly increased expression of CD40, a known marker of pro-inflammatory M1 activation of microglia and macrophages. To further examine whether NAC-induced decreases in nicotine seeking involve suppression of TNFα, we manipulated a downstream mediator of this pathway, nuclear factor kappa B (NF-kB). Considering the putative role of NF-κB in learning, memory, and synaptic plasticity, separate experiments were performed where rats were treated with herpes simplex virus (HSV) vectors designed to increase (HSV-IKKca) or decrease (HSV-IKKdn) NF-κB signaling through interactions with IκB Kinase (IKK). The goal was to examine the role of NF-κB signaling in mediating nicotine seeking behavior and if NF-κB signaling regulates GLT-1 expression. HSV-IKKdn alone and in combination with NAC inhibited cue-induced nicotine reinstatement, while HSV-IKKca blocked the attenuating effect of NAC on reinstatement. Interestingly, both HSV-IKKdn and HSV-IKKca, regardless of NAC treatment, inhibited GLT-1 expression. Taken together, these results suggest that while GLT-1 may be a conserved neurobiological substrate underlying relapse vulnerability across drugs of abuse, immunomodulatory mechanisms may regulate drug-induced alterations in glutamatergic plasticity that mediate cue-induced drug-seeking behavior through GLT-1-independent mechanisms.
ContributorsNamba, Mark Douglas (Author) / Gipson-Reichardt, Cassandra D (Thesis advisor) / Conrad, Cheryl D. (Committee member) / Neisewander, Janet L (Committee member) / Arizona State University (Publisher)
Created2019
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 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
Description
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
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 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