Indiana University-Purdue University Indianapolis (IUPUI) / Alcohol-paired cues invigorate alcohol-seeking and drinking behaviors in both rodents and individuals with alcohol use disorder (AUD). Additionally, genetic susceptibility plays a key role in alcohol addiction behaviors. Alcohol preferring (P) rats model both genetic vulnerability and symptoms of AUD. The basolateral amygdala (BLA), prefrontal cortex (PFC), hippocampus (HC) and nucleus accumbens (NA) are important brain regions involved in cued alcohol seeking. These regions are interconnected and their functional connections are hypothesized to be critical in the expression of motivated behaviors. Electrophysiological recordings in these four regions were collected in P rats engaged in a cued alcohol task. Data were filtered in the theta band (5-11 Hz) and segregated by behavioral epoch. The phase locking index γ was computed and used to measure strength of phase locking between signals from any two brain regions. The cross correlation between the amplitude of two signals was used to determine directionality. PFC-NA synchrony increased after stimuli presentation and remained elevated, relative to baseline synchrony. PFC-NA synchrony was also stronger for trials in which the animal made three or more lever presses (rewarded; R), compared to trials in which the animal responded fewer than three times (not-rewarded; NR). During lever pressing, PFC-BLA, NA-HC and PFC-HC synchrony was stronger after presentation of the DS+, in R compared to NR trials. NA-HC and PFC-BLA synchrony was stronger when responses were withheld in extinction, relative to conditioning. These data inform our knowledge of how corticolimbic connections are involved in cued ethanol seeking behaviors.

Indiana University-Purdue University Indianapolis (IUPUI) / Introduction: Externalizing disorders such as attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD) have a high prevalence rate in both children of alcoholics and in those with prenatal alcohol exposure (PAE). These disorders are also predictors of alcohol dependence (alcdep), heritable, and share an underlying genetic liability with alcdep. Furthermore, a mother who drinks while pregnant is likely to be alcohol dependent (AD), and vice-versa. This study incorporated these factors into one model, including as well as a measure of broad genetic risk for ADHD and alcdep to test for the contributions of these effects simultaneously. An independent sample was used to confirm the results for PAE and broad genetic risk. The hypothesis is that PAE will increase the risk to ADHD but not to CD or ODD. Methods: Each of these factors was evaluated independently to test if that effect on its own, significantly contributed to each disorder. Another model included several demographic covariates, to determine which of these environmental effects also contributed to the disorder. The final model for each disorder included environmental effects along with the primary effects of interest. Results: PAE resulted in increased risk for the inattentive (INATT) sub-type of ADHD and conduct disorder (CD) in the discovery sample and for the hyperactive-impulsive (HYPIMP), INATT and CD in the replication sample. PAE and the PAE*maternal alcohol dependence interaction increased the risk for ADHD and INATT. A broad genetic risk for ADHD was associated with all disorders except HYPIMP in the replication sample. Conclusion: This study further supports the trending evidence of a unique etiology of ADHD in those with PAE, and more specifically, that INATT and HYPIMP are affected according to two different mechanisms of action, independent of a genetic contribution due to either ADHD or alcohol dependence, both of which also were associated with a risk for INATT. The contribution of PAE to INATT and CD were the only consistent results across all definitions of alcohol exposure and in both datasets, indicating that PAE is a veritable risk for INATT and CD.

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Research shows corporal punishment is associated with negative outcomes in offspring. These negative outcomes can present themselves during childhood and emerging adulthood. One negative consequence can be alcohol abuse. The consequences of alcohol abuse in emerging adults are reasons to research corporal punishment’s effects to support positive parental discipline. The current study examined the relationship between past-year corporal punishment and alcohol abuse in the emerging adulthood population. Results of the current study showed corporal punishment was correlated positively with alcohol use, externalizing problems, and authoritarian parenting style, and negatively correlated with maternal authoritative parenting style and permissive parenting style. Males reported higher amounts of paternal corporal punishment and higher amounts of alcohol consumption. Finally, it was determined that risk factors for alcohol abuse included male gender, Caucasian ethnicity, and positive history of family alcohol abuse, and that psychopathology mediated the relationship between corporal punishment and alcohol use and abuse.

The development of multiple theoretical models and measures of impulsivity has led to inconsistent use of this term and disagreement regarding the most salient predictors of alcohol-related outcomes. The present study examined whether self-report and behavioral measures of impulsivity measure the same construct and how eight conceptually distinct facets of impulsivity relate to alcohol-related outcomes. Participants completed measures and tasks to assess alcohol use, alcohol problems, trait impulsivity, and behavioral impulsivity. The UPPS-P and behavioral measures of impulsivity were largely uncorrelated with each other. Negative urgency and alcohol use emerged as direct predictors of alcohol-related problems. Lack of premeditation demonstrated an indirect effect on alcohol-related problems. Results support previous research suggesting behavioral and self-report measures of impulsivity do not assess the same construct. Further, results suggest that negative urgency may be the most predictive of alcohol-related problems when accounting for self-report and behavioral components of impulsivity.

特異なルテニウムが触媒する"Borrowing hydrogen"のコンセプトに基づく有機反応を開発した。まず、Ru/JOSIPHOS触媒を用いて、1,2-ジオールとアミンの反応から光学活性β-アミノアルコールを最高99%収率ならびに77% eeで得ることに成功した。本反応は新規であり、その反応機構についても明らかにした。さらに、RuCl2(PPh3)3/DPEphos/K3PO4を組み合わせた触媒を用いることで、アルコールをアルキル化剤に用いるインドールの3位選択的アルキル化反応を達成した。高効率かつ広いタイプの基質に適用できる。 / Several novel ruthenium-catalyzed "borrowing hydrogen"-based organic reaction has been developed. For very first time optically active β-amino alcohols can be sinthesized directy by reaction of 1,2-diol and coressponding amine under Ru/JOSIPHOS catalysis in up to 99% yield and 77% ee. Since this reaction is very new, intensive investigation of the reaction mechanism was also carried out. Meanwhile, combination of RuCl2(PPh3)3/DPEphos/K3PO4 was found to be effective catalyst for alkylation of indole with alcohol as an alkylating reagent. This catalysis was highly reactive to give the corresponding alkylated indole in excellent yield for almost all types of indoles and alcohols substrates. / 博士(工学) / Doctor of Philosophy in Engineering / 同志社大学 / Doshisha University

Alcohol use has been a longstanding problem on college campuses. Despite the efforts National Institute on Alcohol Abuse and Alcoholism and the commissioned Task Force on College Drinking (2002), there has been a recent rise in the number of alcohol related arrests and violations on college campuses. Within the high-risk mandated student population, the most successful programs utilize motivational enhancement strategies, such as the Brief Alcohol Screening and Intervention for College Students (BASICS). Likely due to financial constraints, an important issue that has been raised is the limited availability of validated methods for alcohol prevention and intervention on college campuses. The purpose of this study was to examine the effectiveness of the digitally assisted Expectancy Challenge Alcohol Literacy Curriculum (ECALC) by direct comparison of the ECALC to an already well-established treatment (i.e., BASICS) in an effort to reduce problematic alcohol use and related negative consequences among mandated college students. The role of the digital enhancements is to decrease time and resources necessary for training facilitators and aid in widespread implementation. Analyses revealed significant reductions on all four positive alcohol expectancies subscales for those in the ECALC condition and a significant intervening effect for the expectancies of Sociability and Liquid Courage. Results also revealed that for both males and females, those in the ECALC condition demonstrated significantly greater reductions in frequency of alcohol use (i.e., number of drinking days per month) and comparable reductions in typical (i.e., mean BAC, average drinks per sitting, average drinks per week) and heavy alcohol use (i.e., peak BAC, peak drinks per sitting, number of binge episodes) at follow-up when compared to those in the BASICS condition.

The purpose of this study was to examine the hypocrisy paradigm as an experimental alcohol intervention to determine if participants who complete the hypocrisy paradigm will experience a significant reduction in the number of negative consequences associated with their alcohol use, quantity and frequency of alcohol use, and average and peak eBAC compared to college students in the control condition. Participants were 53 college students randomly assigned to an experimental hypocrisy paradigm intervention or a control condition. Contrary to prediction, the hypocrisy paradigm was not found to be significantly different than the control condition. Exploratory analyses examining within-group differences were conducted. All outcome measures decreased from pre-intervention to follow-up within the hypocrisy paradigm condition. Future directions and implications are discussed.