Matching Items (117)
Description
The use of synthetic cathinones or "bath salts" has risen dramatically in recent years with one of the most popular being Methylendioxypyrovalerone (MDPV). Following the temporary legislative ban on the sale and distribution of this compound , a multitude of other cathinone derivatives have been synthesized. The current study seeks to compare the abuse potential of MDPV with one of the emergent synthetic cathinones 4-methylethcathinone (4-MEC), based on their respective ability to lower current thresholds in an intracranial self-stimulation (ICSS) paradigm. Following acute administration (0.1, 0.5, 1 and 2 mg/kg i.p.) MDPV was found to significantly lower ICSS thresholds at all doses tested (F4,35=11.549, p<0.001). However, following acute administration (0.3,1,3,10,30 mg/kg i.p) 4-MEC produced no significant ICSS threshold depression (F5,135= 0.622, p = 0.684). Together these findings suggest that while MDPV may possess significant abuse potential, other synthetic cathinones such as 4-MEC may have a drastically reduced potential for abuse.
ContributorsWegner, Scott Andrew (Author) / Olive, M. Foster (Thesis director) / Presson, Clark (Committee member) / Sanabria, Federico (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2013-05
Description
Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the hippocampus with adeno- associated viral vectors containing the coding sequence for short interfering (si)RNA directed against BDNF or a scrambled sequence (Scr), with both containing the coding information for green fluorescent protein to aid in anatomical localization. Rats were then chronically restrained (wire mesh, 6h/d/21d) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trial. Rats in the Str-Imm group, regardless of viral vector contents, committed more errors in the spatial reference memory domain than did non-stressed controls. Importantly, the typical improvement in spatial memory following recovery from chronic stress was blocked with the siRNA against BDNF, as Str-Rec-siRNA performed worse on the RAWM compared to the non-stressed controls or Str-Rec-Scr. These effects were specific for the reference memory domain as repeated entry errors that reflect spatial working memory were unaffected by stress condition or viral vector contents. These results demonstrate that hippocampal BDNF is necessary for the recovery from stress-induced hippocampal dependent spatial memory deficits in the reference memory domain.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Taylor, Sara (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
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
Research has shown that a developmental process of maturing out of alcohol involvement occurs during young adulthood, and that this process is related to both young adult role transitions (e.g., marriage) and personality developmental (e.g., decreased disinhibition and neuroticism). The current study extended past research by testing whether protective marriage and personality effects on maturing out were stronger among more severe late adolescent drinkers, and whether protective marriage effects were stronger among those who experienced more personality development. Parental alcoholism and gender were tested as moderators of marriage, personality, and late adolescent drinking effects on maturing out; and as distal predictors mediated by these effects. Participants were a subsample (N = 844; 51% children of alcoholics; 53% male, 71% non-Hispanic Caucasian, 27% Hispanic; Chassin, Barrera, Bech, & Kossak-Fuller, 1992) from a larger longitudinal study of familial alcoholism. Hypotheses were tested with latent growth models characterizing alcohol consumption and drinking consequence trajectories from late adolescence to adulthood (age 17-40). Past findings were replicated by showing protective effects of becoming married, sensation-seeking reductions, and neuroticism reductions on the drinking trajectories. Moderation tests showed that protective marriage effects on the drinking trajectories were stronger among those with higher pre-marriage drinking in late adolescence (i.e., higher growth intercepts). This might reflect role socialization mechanisms such that more severe drinking produces more conflict with the demands of new roles (i.e., role incompatibility), thus requiring greater drinking reductions to resolve this conflict. In contrast, little evidence was found for moderation of personality effects by late adolescent drinking or for moderation of marriage effects by personality. Parental alcoholism findings suggested complex moderated mediation pathways. Parental alcoholism predicted less drinking reduction through decreasing the likelihood of marriage (mediation) and muting marriage's effect on the drinking trajectories (moderation), but parental alcoholism also predicted more drinking reduction through increasing initial drinking in late adolescence (mediation). The current study provides new insights into naturally occurring processes of recovery during young adulthood and suggests that developmentally-tailored interventions for young adults could harness these natural recovery processes (e.g., by integrating role incompatibility themes and addressing factors that block role effects among those with familial alcoholism).
ContributorsLee, Matthew R. (Author) / Chassin, Laurie (Thesis advisor) / Corbin, William R. (Committee member) / Mackinnon, David P (Committee member) / Presson, Clark C. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Past literature has indicated that the majority of people with alcohol problems never seek treatment and that this is especially true of women. Relatively few studies have investigated how different types of alcohol-related consequences longitudinally predict men and women's perceived need for treatment and their utilization of treatment services. The current study sought to expand the literature by examining whether gender moderates the links between four frequently endorsed types of consequences and perceived need for or actual utilization of treatment. Two-hundred thirty-seven adults ages 21-36 completed a battery of questionnaires at two time points five years apart. Results indicated that there were four broad types of consequences endorsed by both men and women. Multiple-group models and Wald chi square tests indicated that there were no significant relationships between consequences and treatment outcomes. No gender moderation was found but post-hoc power analyses indicated that the study was underpowered to detect moderation. Researchers need to continue to study factors that predict utilization of alcohol treatment services and the process of recovery so that treatment providers can better address the needs of people with alcohol-related consequences in the areas of referral procedures, clinical assessment, and treatment service provision and planning.
ContributorsBeltran Gonzalez, Iris (Author) / Chassin, Laurie (Thesis advisor) / Tein, Jenn-Yun (Committee member) / Corbin, William (Committee member) / Barrera, Jr., Manuel (Committee member) / Arizona State University (Publisher)
Created2013
Description
Accumulating evidence implicates exposure to adverse childhood experiences in the development of hypocortisolism in the long-term, and researchers are increasingly examining individual-level mechanisms that may underlie, exacerbate or attenuate this relation among at-risk populations. The current study takes a developmentally and theoretically informed approach to examining episodic childhood stressors, inherent and voluntary self-regulation, and physiological reactivity among a longitudinal sample of youth who experienced parental divorce. Participants were drawn from a larger randomized controlled trial of a preventive intervention for children of divorce between the ages of 9 and 12. The current sample included 159 young adults (mean age = 25.5 years; 53% male; 94% Caucasian) who participated in six waves of data collection, including a 15-year follow-up study. Participants reported on exposure to negative life events (four times over a 9-month period) during childhood, and mothers rated child temperament. Six years later, youth reported on the use of active and avoidant coping strategies, and 15 years later, they participated in a standardized psychosocial stress task and provided salivary cortisol samples prior to and following the task. Path analyses within a structural equation framework revealed that a multiple mediation model best fit the data. It was found that children with better mother-rated self-regulation (i.e. low impulsivity, low negative emotionality, and high attentional focus) exhibited lower total cortisol output 15 years later. In addition, greater self-regulation in childhood predicted greater use of active coping in adolescence, whereas a greater number of negative life events predicted increased use of avoidant coping in adolescence. Finally, a greater number of negative events in childhood predicted marginally lower total cortisol output, and higher levels of active coping in adolescence were associated with greater total cortisol output in young adulthood. Findings suggest that children of divorce who exhibit better self-regulation evidence lower cortisol output during a standardized psychosocial stress task relative to those who have higher impulsivity, lower attentional focus, and/or higher negative emotionality. The conceptual significance of the current findings, including the lack of evidence for hypothesized relations, methodological issues that arose, and issues in need of future research are discussed.
ContributorsHagan, Melissa (Author) / Luecken, Linda (Thesis advisor) / MacKinnon, David (Committee member) / Wolchik, Sharlene (Committee member) / Doane, Leah (Committee member) / Arizona State University (Publisher)
Created2013
Description
Juvenile offenders suffer from substance use disorders at higher rates than adolescents in the general public. Substance use disorders also predict an increased risk for re-offending. Therefore, it is important that these juveniles, in particular, receive the appropriate substance use disorder treatment. The present study used logistic regression to test whether race/ethnicity would moderate the match between substance use disorder diagnosis and the receipt of a substance use disorder related service in a sample of male, serious juvenile offenders. Results showed that among those with a substance use disorder diagnosis, there were no race/ethnicity differences in the receipt of the appropriate service. However, among those without a substance use disorder diagnosis, non-Hispanic Caucasians were more likely to receive substance use service than were Hispanics or African-Americans. Post-hoc analyses revealed that when using a broader definition of substance use problems, significant differences by race/ethnicity in the prediction of service receipt were only observed at low levels of substance use problems. These findings shed light on how race/ethnicity may play a role in the recommendation of substance use disorder services in the juvenile justice system.
ContributorsMansion, Andre (Author) / Chassin, Laurie (Thesis advisor) / Dishion, Thomas (Committee member) / Knight, George (Committee member) / Arizona State University (Publisher)
Created2013
Description
The hypothalamus pituitary adrenal (HPA) axis and the human genome are important components of the biological etiology of externalizing disorders. By studying the associations between specific genetic variants, diurnal cortisol, and externalizing symptoms we can begin to unpack this complex etiology. It was hypothesized that genetic variants from the corticotropine releasing hormone receptor 1 (CRHR1), FK506 binding protein 51 (FKBP5), catechol-O-methyl transferase (COMT), and dopamine transporter (DAT1) genes and diurnal cortisol intercepts and slopes would separately predict externalizing symptoms. It was also hypothesized that genetic variants would moderate the association between cortisol and externalizing. Participants were 800 twins (51% boys), 88.5% Caucasian, M=7.93 years (SD=0.87) participating in the Wisconsin Twin Project. Hierarchical Linear Modeling (HLM) was used to separate the variance associated with state and trait cortisol measured across three consecutive days and trait cortisol measures were used. There were no main effects of genes on externalizing symptoms. The evening cortisol intercept, the morning cortisol slope and the evening cortisol slope predicted externalizing, but only in boys, such that boys with higher cortisol and flatter slopes across the day also had more externalizing symptoms. The morning cortisol intercept and CRHR1 rs242924 interacted to predict externalizing in both boys and girls, with GG carriers significantly higher compared to TT carriers at one standard deviation below the mean of morning cortisol. For boys only there was a significant interaction between the DAT1 variable number tandem repeat (VNTR) and the afternoon slope and a significant slope for 9/9 carriers and 9/10 carriers such that when the slope was more steep, boys carrying a nine had fewer externalizing symptoms but when the slope was less steep, they had more. Results confirm a link between diurnal trait cortisol and externalizing in boys, as well as moderation of that association by genetic polymorphisms. This is the first study to empirically examine this association and should encourage further research on the biological etiology of externalizing disorder symptoms.
ContributorsSwann, Gregory (Author) / Lemery-Chalfant, Kathryn (Thesis advisor) / Chassin, Laurie (Committee member) / Doane-Sampey, Leah (Committee member) / Arizona State University (Publisher)
Created2012
Description
The present study utilized longitudinal data from a high-risk community sample (n= 377; 166 trauma-exposed; 54% males; 52% children of alcoholics; 73% non-Hispanic/Latino Caucasian; 22% Hispanic/Latino; 5% other ethnicity) to test a series of hypotheses that may help explain the risk pathways that link traumatic stress, posttraumatic stress disorder (PTSD) symptomatology, and problematic alcohol and drug use. Specifically, this study examined whether pre-trauma substance use problems increase risk for trauma exposure (the high-risk hypothesis) or PTSD symptoms (the susceptibility hypothesis), whether PTSD symptoms increase risk for later alcohol/drug problems (the self-medication hypothesis), and whether the association between PTSD symptoms and alcohol/drug problems is due to shared risk factors (the shared vulnerability hypothesis). This study also examined the roles of gender and ethnicity in these pathways. A series of logistic and negative binomial regressions were performed in a path analysis framework. A composite pre-trauma family adversity variable was formed from measures of family conflict, family life stress, parental alcoholism, and other parent psychopathology. Results provided the strongest support for the self-medication hypothesis, such that PTSD symptoms predicted higher levels of later alcohol and drug problems among non-Hispanic/Latino Caucasian participants, over and above the influences of pre-trauma family adversity, pre-trauma substance use problems, trauma exposure, and demographic variables. Results partially supported the high-risk hypothesis, such that adolescent substance use problems had a marginally significant unique effect on risk for assaultive violence exposure but not on overall risk for trauma exposure. There was no support for the susceptibility hypothesis, as pre-trauma adolescent substance use problems did not significantly influence risk for PTSD diagnosis/symptoms over and above the influence of pre-trauma family adversity. Finally, there was little support for the shared vulnerability hypothesis. Neither trauma exposure nor preexisting family adversity accounted for the link between PTSD symptoms and later substance use problems. These results add to a growing body of literature in support of the self-medication hypothesis. Findings extend previous research by showing that PTSD symptoms may influence the development of alcohol and drug problems over and above the influence of trauma exposure itself, preexisting family risk factors, and baseline levels of substance use.
ContributorsHaller, Moira (Author) / Chassin, Laurie (Thesis advisor) / Davis, Mary (Committee member) / Pina, Armando (Committee member) / Tein, Jenn-Yun (Committee member) / Arizona State University (Publisher)
Created2014
Description
Levels of heavy episodic drinking peak during emerging adulthood and contribute to the experience of negative consequences. Previous research has identified a number of trait-like personality characteristics that are associated with drinking. Studies of the Acquired Preparedness Model have supported positive expectancies, and to a lesser extent negative expectancies, as mediators of the relation between trait-like characteristics and alcohol outcomes. However, expectancies measured via self-report may reflect differences in learned expectancies in spite of similar alcohol-related responses, or they may reflect true individual differences in subjective responses to alcohol. The current study addressed this gap in the literature by assessing the relative roles of expectancies and subjective response as mediators within the APM in a sample of 236 emerging adults (74.7% male) participating in a placebo-controlled alcohol challenge study. The study tested four mediation models collapsed across beverage condition as well as eight separate mediation models with four models (2 beverage by 2 expectancy/subjective response) for each outcome (alcohol use and alcohol-related problems). Consistent with previous studies, SS was positively associated with alcohol outcomes in models collapsed across beverage condition. SS was also associated with positive subjective response in collapsed models and in the alcohol models. The hypothesized negative relation between SS and sedation was not significant. In contrast to previous studies, neither stimulation nor sedation predicted either weekly drinking or alcohol-related problems. While stimulation and alcohol use appeared to have a positive and significant association, this relation did not hold when controlling for SS, suggesting that SS and stimulation account for shared variability in drinking behavior. Failure to find this association in the placebo group suggests that, while explicit positive expectancies are related to alcohol use after controlling for levels of sensation seeking, implicit expectancies (at least as assessed by a placebo manipulation) are not. That the relation between SS and stimulation held only in the alcohol condition in analyses separate by beverage condition indicates that sensation seeking is a significant predictor of positive subjective response to alcohol (stimulation), potentially above and beyond expectancies.
ContributorsScott, Caitlin (Author) / Corbin, William (Thesis advisor) / Shiota, Michelle (Committee member) / Chassin, Laurie (Committee member) / Arizona State University (Publisher)
Created2012