IU Indianapolis ScholarWorks :: Browsing by Author "Grahame, Nicholas J."

Browsing by Author "Grahame, Nicholas J."

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A critical review of front-loading: A maladaptive drinking pattern driven by alcohol's rewarding effects
(Wiley, 2022) Ardinger, Cherish E.; Lapish, Christopher C.; Czachowski, Cristine L.; Grahame, Nicholas J.; Psychology, School of Science
Front‐loading is a drinking pattern in which alcohol intake is skewed toward the onset of reward access. This phenomenon has been reported across several different alcohol self‐administration protocols in a wide variety of species, including humans. The hypothesis of the current review is that front‐loading emerges in response to the rewarding effects of alcohol and can be used to measure the motivation to consume alcohol. Alternative or additional hypotheses that we consider and contrast with the main hypothesis are that: (1) front‐loading is directed at overcoming behavioral and/or metabolic tolerance and (2) front‐loading is driven by negative reinforcement. Evidence for each of these explanations is reviewed. We also consider how front‐loading has been evaluated statistically in previous research and make recommendations for defining this intake pattern in future studies. Because front‐loading may predict long‐term maladaptive alcohol drinking patterns leading to the development of alcohol use disorder (AUD), several future directions are proposed to elucidate the relationship between front‐loading and AUD.
Achieving pharmacologically relevant IV alcohol self-administration in the rat
(2012-09-27) Windisch, Kyle Allyson; Czachowski, Cristine L.; Grahame, Nicholas J.; Kosobud, Ann E. K.
Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be quite separate temporally from time of intake) and the more temporally “relevant” effects (primarily olfactory and taste) that bridge the time from intake to the onset of the pharmacological effects. Dissociating these effects is essential to untangling the neurologic underpinnings of alcohol abuse and dependence. Intravenous self-administration of ethanol allows for controlled and precise dosing, bypasses first order absorption kinetics allowing for a faster onset of pharmacologic effects, and eliminates the confounding “non-pharmacological” effects associated with oral consumption. Intravenous self-administration of ethanol has been reliably demonstrated in both mouse and human experimental models; however, consistent intravenous self-administration of pharmacologically relevant levels of ethanol remains elusive in the rat. Previous work has demonstrated reliable elevated intravenous ethanol self administration using a compound reinforcer of oral sucrose and intravenous ethanol. The present study sought to elucidate the role of each component of this reinforcer complex using a multiple schedule study design. Male P rats had free access to both food and water during all intravenous self-administration sessions and all testing was performed in conjunction with the onset of the dark cycle. Once animals achieved stable operant responding on both levers for an orally delivered 1% sucrose solution (1S) on a FR4 schedule, surgery was conducted to implant an indwelling jugular catheter. Animals were habituated to the attachment of infusion apparatus and received twice daily sessions for four days to condition each lever to its associated schedule. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5 minute components. During one component only oral 1S was presented, while in the second component a compound reinforcer of oral 1S + IV 20% ethanol was presented (25 mg/kg/injection). Both levers were extended into the chamber during the session, with the active lever/schedule alternating as the session progressed across components. Average ethanol intake was 0.47 ± 0.04 g/kg. A significant increase in sucrose only reinforcers and sucrose lever error responding was found suggesting that sucrose not ethanol is responsible for driving overall responding. The current findings suggest that the existing intravenous ethanol self-administration methodology remains aversive in the rat.
Acute drug effects on habitual and non-habitual responding in crossed high alcohol preferring mice
(Springer Nature, 2018-07) Houck, Christa A.; Grahame, Nicholas J.; Psychology, School of Science
RATIONALE: Drug reward plays a central role in acquiring drug-seeking behavior. However, subjects may continue using drugs despite negative consequences because self-administration becomes habitual, and divorced from outcome values. Although a history of drug and alcohol use expedite habit acquisition, and in spite of the fact that self-administration leads to intoxication, the acute effects of drugs on habitual responding are not well understood. OBJECTIVES: We sought to observe how acute ethanol and amphetamine affect the balance between habitual and goal-directed behavior, as measured by a fluid-reinforced operant conditioning task. METHODS: Selectively bred crossed high-alcohol-preferring (cHAP) mice were trained on an operant conditioning task reinforced on a variable interval schedule with 1% banana solution, which was subsequently devalued via LiCl pairing in half the animals. Ethanol (1.0 g/kg), amphetamine (2.0 mg/kg), or saline was administered prior to a post-devaluation test. RESULTS: Overall, mice showed habitual behavior, but when divided into high- or low-responding groups based on training response rates, saline-treated, low-responding animals devalued, while saline-treated high-responding animals did not. Furthermore, amphetamine elicited devaluation even in high-responding animals, while ethanol prevented devaluation even in low-responding animals. CONCLUSIONS: These data show that ethanol shifts animals toward behaving habitually. This may illuminate why alcohol-intoxicated individuals display impaired judgment about the relative merits of drinking, and potentially serve as a mechanism by which intoxicated subjects resume previously devalued behaviors, such as comorbid drug use. These findings also show that high variable interval response rates facilitate a shift from goal-directed to habitual behavior.
Adolescent and Adult Two-Bottle Choice Ethanol Drinking and Adult Impulsivity in Genetically Selected High-Alcohol Preferring Mice
(2012-09-20) O'Tousa, David Scott; Grahame, Nicholas J.; Czachowski, Cristine; Boehm II, Stephen L.
Abuse of alcohol during adolescence continues to be a problem, and it has been shown that earlier onset of drinking predicts increased alcohol abuse problems later in life. High levels of impulsivity have been demonstrated to be characteristic of alcoholics, and impulsivity has also been shown to predict later alcohol use in teenage subjects, showing that impulsivity may be an inherent underlying biological process that precedes the development of alcohol use disorders. These experiments examined adolescent drinking in a high-drinking, relatively impulsive mouse population, and assessed its effects on adult drinking and adult impulsivity. Experiment 1: Selectively bred High-Alcohol Preferring (HAP II) mice, which are shown to be highly impulsive, were given either alcohol (free choice access) or water only for two weeks during middle adolescence or adulthood. All mice were given free choice access to alcohol following 30 days without access, in adulthood. Experiment 2: Adolescent HAP II mice drank alcohol and water, or water alone, for two weeks, and were then trained to perform a delay discounting task as adults to measure impulsivity. In each experiment, effects of volitional ethanol consumption on later behavior were assessed. We expected adolescent alcohol exposure to increase subsequent drinking and impulsivity. Adolescent mice consumed significant quantities of ethanol, reaching average blood ethanol concentrations (BECs) of 142 mg/dl in Experiment 1 and 108 mg/dl in Experiment 2. Adult mice reached average BECs of 154 mg/dl in Experiment 2. Mice pre-exposed to alcohol in either adolescence or adulthood showed a transient increase in ethanol consumption, but we observed no differences in impulsivity in adult mice as a function of whether mice drank alcohol during adolescence. These findings indicate that HAP II mice drink intoxicating levels of alcohol during both adolescence and adulthood, and that this volitional intake has long-term effects on subsequent drinking behavior. Nonetheless, this profound exposure to alcohol during adolescence does not increase impulsivity in adulthood, indicating that long-term changes in drinking are mediated by mechanisms other than impulsivity. Importantly, this research demonstrates that the HAP II mouse is a good candidate for a model of heavy adolescent alcohol consumption.
Affective traits and adiposity : a prospective, bidirectional analysis of the African American Health study data
(Proquest, 2013) Hawkins, Misty Anne; Stewart, Jesse C.; Rand, Kevin L.; Cyders, Melissa A.; Miller, Douglas K.; Grahame, Nicholas J.
Research indicates that negative affective traits (e.g., depression) are predictors and consequences of excess adiposity. Given that racial minorities and positive affective traits have been underrepresented in past investigations, more prospective studies are needed which examine multiple affective traits in relation to obesity in these populations. The objective of the current study was to investigate the prospective, bidirectional associations between multiple affective traits and multiple adiposity indicators in African Americans using data from the African American Health (AAH) study. The AAH study is a prospective cohort study of African Americans aged 49-65 years at baseline (N = 998). The longest follow-up period in the current study was 9 years (N = 579). Self-reported and measured body mass index (BMI; kg/m2) and body fat percent (BF%) were used as adiposity indicators. Depressive symptoms were assessed with the 11-item Center for Epidemiologic Studies-Depression Scale (CES-D), and anxiety was assessed using the Generalized Anxiety Disorder-2 (GAD-2) scale. Positive affective traits were assessed with the Vitality subscale of the Short Form-36 and Positive Affect subscale from the CES-D. Latent variable path analysis, a structural equation modeling technique, was conducted. Although fit statistics indicated that the models fit the data (RMSEA < .06), examination of the structural paths revealed that the CES-D and GAD-2 were not predictors or consequences of self-reported BMI, measured BMI, or BF% (ps > .05). Likewise, Vitality and CES-D Positive Affect were not related to any adiposity indicator (ps > .05). The results of this prospective cohort study suggest that affective traits are not predictors or consequences of adiposity in middle-aged African Americans and that this group may require obesity prevention or intervention programs with little to no emphasis on affective traits. Possible explanations for the current results include ethnic differences in the mechanistic pathways between affective traits and adiposity.
ALTERATIONS IN THE SEEKING AND SELF-ADMINISTRATION OF ETHANOL AND ANXIETY-LIKE BEHAVIOR FOLLOWING EXPOSURE TO YOHIMBINE IN RATS SELECTIVELY BRED FOR HIGH ALCOHOL INTAKE
(2011-08-16) Bertholomey, Megan Lee; Grahame, Nicholas J.; Czachowski, Cristine; Stewart, Robert; Chester, Julia A.
Stress has been shown to contribute to alcohol drinking; however, inconsistencies in both the clinical and pre-clinical literature speak to the need for better paradigms to study this interaction. The present experiments compared animal models of the propensity to consume ethanol, the selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) rat lines, in their response to yohimbine on ethanol seeking and self-administration and anxiety-like behavior. The P and HAD lines consume similar amounts of ethanol, yet differ in apparent motivation to drink ethanol, in anxiety-like behavior, and response to stress in alcohol drinking. Therefore, it was of interest to determine whether stress may differentially affect ethanol-motivated behaviors between the P and HAD lines. Acute administration of yohimbine, an α-2 adrenoreceptor antagonist that increases anxiety and activate stress systems, increased operant ethanol self-administration and reinstatement of ethanol seeking in P rats, and free-choice ethanol drinking in both P and HAD rats. However, acute yohimbine administration decreased ethanol drinking when given limited access in the home cage, an effect that was diminished by extending the pre-treatment interval or increasing the number of ethanol exposure sessions. Yohimbine did not alter appetitive responding during a non-reinforced trial, nor did yohimbine alter the acquisition of free-choice ethanol drinking. Exposure to alcohol deprivation resulted in modest increases in ethanol intake, but yohimbine did not potentiate this effect. While acute yohimbine administration increased anxiety-like behavior, prior experience with repeated yohimbine exposures or with repeated deprivation periods did not. P rats were shown to be more active and less anxious and to display greater responding during a non-reinforced trial than HAD rats. Taken together, the results of these experiments demonstrate that the timing of yohimbine exposure relative to ethanol access is a critical component to determining its effects on ethanol seeking and self-administration and anxiety-like behavior. Further investigation into the parameters under which stress alters the motivation to seek and consume ethanol between these selectively bred lines is warranted, and future work that incorporates therapeutic agents aimed at reducing stress reactivity and alcohol drinking could elucidate effective strategies in the treatment of alcoholism.
Applicant Reactions to Structuring the Selection Interview
(2013-08-14) Lombard-Sims, Danielle; Hazer, John; Williams, Jane R.; Shermis, Mark D., 1953-; Grahame, Nicholas J.
Initial research on structuring the interview process investigated structure’s impact on the interview’s psychometric properties (e.g., reliability and validity). In contrast, the empirical literature has begun to consider the impact of increased interview structure on job applicant reactions to the interview and the companies that utilize them. Current research has studied the effects of interviewer characteristics on applicant reactions and the effects of different types of selection procedures on applicant fairness reactions. In addition, while studies have examined the impact of applicants’ perceived control on their reactions to selection procedures, few studies have examined this impact specifically for the employment interview. Given the widespread use of the interview in selection, this study adds to current research by focusing on applicant reactions to four elements of the interview identified as being salient to applicants (i.e., the degree to which the interviewee perceives that applicants are asked the same questions, the use of situational or behavioral type questions, controlling the use of ancillary information by the interviewer, and the degree to which questions from the applicant are controlled). In addition, this study focused on need for control as a moderator of the relationships between interview structure and fairness perceptions, recommendation intentions, and acceptance intentions. Participants consisted of 161 students voluntarily participating in three different interviewing scenarios: unstructured, semi-structured, and structured interviewing scenario. The participants completed post-interview measures asking them about their perceptions of fairness, their intention to recommend the company to others, and their intention of accepting an offer if one is made by the company. Although the hypothesized relationships between elements of structure and applicant evaluations of the interview were largely not supported, the results did indicate that student applicants perceived semi-structured and structured interviews to be fairer than unstructured interviews. In addition, the results suggest that more structured interviews may lead to lower behavioral intent to recommend the job to others or accept a job offer. Implications of the results are discussed in terms of how interview structure relates to the candidates’ perception of fairness, recommendation intentions, and acceptance intentions.
Assessing the Efficacy of Acceptance and Commitment Therapy in Reducing Schema-enmeshment in Fibromyalgia Syndrome
(2014-09-04) Steiner, Jennifer Leah; Hirsh, Adam; Bigatti, Silvia M.; Ashburn-Nardo, Leslie; Stewart, Jesse C.; Grahame, Nicholas J.
The presence of a chronic pain condition can have a profound impact on one’s self-concept. Some individuals may have had to make major lifestyle changes. As a result, some people may start to define themselves in terms of their pain, such that their self-schema and pain-schemas become intertwined in a process termed schema-enmeshment. It is thought that schema-enmeshment is related to psychological distress making it a prime target for intervention. Little research has been conducted on interventions to reduce schema-enmeshment. Acceptance-based interventions may be especially appropriate in reducing schema-enmeshment or the connection between self and illness symptoms as these interventions tend to emphasize learning to live with pain and other symptoms and to work toward important life goals rather than continually fighting against the condition and allowing it to control their life. This study is a randomized trial comparing Acceptance and Commitment Therapy (ACT) to education about pain management in a sample of women with Fibromyalgia Syndrome (FMS). The primary aim of this study was to assess the efficacy of ACT in reducing schema-enmeshment between self and pain, as well as enmeshment between self and other symptoms and FMS as a whole. In addition, this study also explored the role of pain acceptance, specifically activity engagement as a mediator of the relationship between treatment group membership and changes in schema-enmeshment. The data was analyzed as an intent-to-treat analysis using the “last measure carried forward” method. Results indicated that the ACT group reported statistically significant differences in self schema-enmeshment with FMS, fatigue, and cognitive symptoms, but not with pain, following the intervention, compared to the educational control group. In each of these cases, the ACT group experienced greater reductions in schema-enmeshment compared to the education group. Interestingly, no statistically significant differences were observed for schema-enmeshment with pain. Statistically significant group differences were also observed for acceptance of pain following the intervention. Finally, a mediational model in which changes in activity engagement (a form of pain acceptance) served as the mediator of the relationship between treatment group and changes in schema-enmeshment with FMS was tested. The model was tested using a bootstrapping method, and results revealed a trend toward a significant indirect effect of changes in activity engagement leading to changes in schema-enmeshment with FMS. Taken together, the results of this study indicate that ACT may be a promising intervention for targeting maladaptive beliefs about the self in relation to illness, especially schema-enmeshment of self with illness and illness symptoms. Additionally, there is evidence that ACT may target key constructs such as activity engagement, which may be related to other cognitive and behavioral changes. Future directions for research and clinical practice related to ACT as an intervention for FMS are discussed in depth.
Assessment of the dopamine system in addiction using positron emission tomography
(2014) Albrecht, Daniel Strakis; Hutchins, Gary D.; Saykin, Andrew J.; Kareken, David A.; Yoder, Karmen K.; Grahame, Nicholas J.
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.
Attachment Avoidance and Depressive Symptoms: A Test of Moderation by Cognitive Abilities
(2014-09-04) Shea, Amanda Marie; Rand, Kevin L.; Stewart, Jesse C.; Cyders, Melissa A.; Ashburn-Nardo, Leslie; Grahame, Nicholas J.
The substantial interpersonal and economic costs of depression make it imperative to better understand the predictors and moderators of depressive symptoms. The ability to use social support protects people from depressive symptoms, but individuals high in attachment avoidance tend not to use others as sources of support. Research has found that attachment avoidance is related to depressive symptoms in some samples but not in others (Mikulincer & Shaver, 2007; Shea, 2011). Thus, there appear to be factors that moderate the relationship between attachment avoidance and depressive symptoms. The present study examined if cognitive abilities that facilitate effective emotion regulation strategies moderate the relationship between attachment avoidance and depressive symptoms. Using a sample of college students, attachment avoidance, cognitive abilities, depressive symptoms, and other indices of psychological distress and well-being were measured and examined for evidence of moderation via hierarchical linear regression. The hypothesis that cognitive abilities moderate the relationship between attachment avoidance and depressive symptoms was not supported (ΔR2 = 0.02, p = .68). Factors contributing to the null findings are discussed and conceptual and methodological suggestions are offered for future research.

Browsing by Author "Grahame, Nicholas J."

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