Indiana University-Purdue University Indianapolis (IUPUI) / Harmful alcohol use is a global concern, which has made research in this area a prime public health interest. Previous research has identified alcohol-related attentional biases (Cox et al., 2002, 2007; Marissen et al., 2006; Streeter et al., 2008) and impulsivity (see Acton, 2003; Dick et al., 2010; Mulder, 2002) as two important predictors that affect alcohol use, seeking, and relapse (Cox et al., 2002; Robbins & Ehrman, 2004). Recent review of the literature has also revealed that there is a significant relationship between these two constructs (Coskunpinar & Cyders, 2013). The current study used college undergraduate social drinkers (at least 3 drinks per week) (n = 42, mean age = 23.27 (SD = 5.21), female: 69.2%) to examine the relationship between specific trait impulsivity facets and alcohol-related attentional biases and to examine how this relationship is affected by measurement type (eye movement, reaction time measures), attentional bias constructs (initial orientation, delayed disengagement), and environmental cues (specifically mood and alcohol olfactory cues). Participants had alcohol-related attentional bias as measured by reaction time (areas of interest: p < .05) and eye-movement data (areas of interest: p < .05), which was not affected by mood, odor, or urgency.

Indiana University-Purdue University Indianapolis (IUPUI) / Prior research indicated a high prevalence of problematic drinking among college students, suggesting a need for more effective screening approaches and treatments. The tendency to act rashly in face of strong emotions (e.g. positive and negative urgency), alcohol cravings, and cue reactivity all have been associated with problematic alcohol use. However, no studies have examined the interactive effects of alcohol cravings, urgency, and cue reactivity. I hypothesized that alcohol cravings will be associated with greater problematic drinking among individuals with higher levels of (1) urgency, (2) cue reactivity, and (3) cue reactivity and urgency. Data were collected from a sample (final n = 240) of college students through a survey, which consisted of measures of urgency, problematic drinking, and alcohol cravings. On the survey, participants were also exposed to alcohol and non-alcohol pictures, after which they assessed their level of cue reactivity. Results were examined using multiple regression and simple slope analyses. Results provided partial support for our hypotheses. Alcohol cravings were associated with greater problematic drinking at lower levels of negative urgency (b = 7.36, p< 0.001). Furthermore, alcohol cravings were most strongly associated with problematic drinking at high levels of cue reactivity and low levels of negative urgency (b = 8.69, p<0.001), and at low levels of cue reactivity and high levels of positive urgency (b = 6.56, p<0.001). These findings emphasize the importance of considering urgency and cue reactivity in understanding how alcohol cravings create risk for problematic drinking.

Indiana University-Purdue University Indianapolis (IUPUI) / Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is found in heavy alcohol users. Negative urgency is a personality trait reflecting the tendency to act rashly in response to negative emotional states, and is associated with problematic alcohol consumption. The current study examined the relationship between negative urgency and HPA axis functioning following (1) negative mood induction and (2) intravenous alcohol administration among heavy social drinkers (proposed n = 40). I hypothesized the following: (1) Negative mood induction would result in an increase of cortisol release as compared to neutral mood induction; (1a) Negative urgency would be related to increased cortisol release in response to negative mood induction; (1b) Negative urgency would partially mediate the relationship between mood induction and cortisol release; (2) Acute IV alcohol administration would result in increased cortisol levels in the neutral mood condition, but decreased cortisol levels in the negative mood condition; and (2a) Negative urgency would be related to the suppression of cortisol release in the negative mood condition in response to acute IV alcohol administration. Repeated measures analyses of variance, the PROCESS macro, and paired samples t-tests were used to examine study hypotheses. Hypotheses were largely unsupported. Writing mood induction procedures reduced salivary cortisol levels in negative mood (t(35)= 2.49, p= 0.02) and there was a trend decrease in neutral mood (t(35)= 1.87, p= 0.07). Alcohol administration also reduced salivary cortisol levels in both negative mood (t(35)= 3.99, p< 0.01) and neutral mood (t(35)= 2.60, p= 0.01). However, salivary cortisol changes were no different than typical circadian patterns in response to mood induction (t(231)= 0.37, p=0.71) or in response to acute alcohol administration (t(231)= 0.44, p= 0.64). Negative urgency had a trend main effect on salivary cortisol level in response to acute IV alcohol administration, such that those higher in negative urgency were more similar to typical circadian patterns (F(19,28)= 1.59, p=0.13). This could serve as preliminary support for a psychological mechanism for the alcohol sensitivity hypothesis. Overall these findings suggest the current study failed to sufficiently manipulate salivary cortisol levels. Future studies should consider methodological techniques when exploring these relationships, including IV compared to oral alcohol administration, mood compared to stress manipulations, and cortisol compared to other HPA axis biomarkers.

Indiana University-Purdue University Indianapolis (IUPUI) / Drug addiction is a behavioral disorder characterized by impulsive behavior and continued intake of drug in the face of adverse consequences. Millions of people suffer the financial and social consequences of addiction, and yet many of the current therapies for addiction treatment have limited efficacy. Therefore, there is a critical need to characterize the neurobiological substrates of addiction in order to formulate better treatment options. In the first chapter, the striatal dopamine system is interrogated with [11C]raclopride PET to assess differences between chronic cannabis users and healthy controls. The results of this chapter indicate that chronic cannabis use is not associated with a reduction in striatal D2/D3 receptor availability, unlike many other drugs of abuse. Additionally, recent cannabis consumption in chronic users was negatively correlated with D2/D3 receptor availability. Chapter 2 describes a retrospective analysis in which striatal D2/D3 receptor availability is compared between three groups of alcohol-drinking and tobacco-smoking subjects: nontreatment-seeking alcoholic smokers, social-drinking smokers, and social-drinking non-smokers. Results showed that smokers had reduced D2/D3 receptor availability throughout the striatum, independent of drinking status. The results of the first two chapters suggest that some combustion product of marijuana and tobacco smoke may have an effect on striatal dopamine concentration. Furthermore, they serve to highlight the effectiveness of using baseline PET imaging to characterize dopamine dysfunction in addictions. The final chapter explores the use of [18F]fallypride PET in a proof-of-concept study to determine whether changes in cortical dopamine can be detected during a response inhibition task. We were able to detect several cortical regions of significant dopamine changes in response to the task, and the amount of change in three regions was significantly associated with task performance. Overall, the results of Chapter 3 validate the use of [18F]fallypride PET to detect cortical dopamine changes during a impulse control task. In summary, the results reported in the current document demonstrate the effectiveness of PET imaging as a tool for probing resting and activated dopamine systems in addiction. Future studies will expand on these results, and incorporate additional methods to further elucidate the neurobiology of addiction.

Indiana University-Purdue University Indianapolis (IUPUI) / Losing a job or a significant other are examples of incentive shifts that result in negative emotional reactions. The occurrence of negative life events is associated with increased drinking, and alleviation of negative emotions has been cited as a drinking motive for individuals with problematic drinking patterns (Keyes et al., 2011; Adams et al., 2012). Further, there is evidence that certain genotypes drink alcohol in response to stressful negative life events (Blomeyer et al., 2008; Covault et al., 2007). It is possible that shared genetic factors contribute to both alcohol drinking and emotional reactivity, but there is a critical need for this relationship to be understood. The first aim of this proposal will use an incentive downshift paradigm to address whether emotional reactivity is elevated in mice predisposed to drink alcohol. The second aim of this proposal will address if reactivity to an incentive shift can result in rash action using a differential reinforcement of low rates of responding task, and whether this response is also associated with a predisposition for high drinking. The third aim of this proposal will investigate if experimenter administered ethanol reduces contrast effects, and if an incentive shift increases ethanol consumption in a high drinking line. The overall goal of this proposal is to investigate whether reactivity to incentive shift is an important mechanism underlying alcohol drinking in these mice, and the role an incentive shift may play in producing rash action and influencing ethanol consumption.