Browsing by Subject "Addiction"

Now showing 1 - 10 of 29
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    Addiction to indoor tanning: Relation to anxiety, depression, and substance use
    (AMA, 2010-04-01) Mosher, Catherine E.; Danoff-Burg, Sharon
    To assess the prevalence of addiction to indoor tanning among college students and its association with substance use and symptoms of anxiety and depression.Two written measures, the CAGE (Cut down, Annoyed, Guilty, Eye-opener) Questionnaire, used to screen for alcoholism, and the Diagnostic and Statistical Manual of Mental Disorders(Fourth Edition, Text Revision) (DSM-IV-TR) criteria for substance-related disorders, were modified to evaluate study participants for addiction to indoor tanning. Standardized self-report measures of anxiety, depression, and substance use also were administered.A large university (approximately 18 000 students) in the northeastern United States.A total of 421 college students were recruited from September through December 2006.Self-reported addiction to indoor tanning, substance use, and symptoms of anxiety and depression.Among 229 study participants who had used indoor tanning facilities, 90 (39.3%) met DSM-IV-TR criteria and 70 (30.6%) met CAGE criteria for addiction to indoor tanning. Students who met DSM-IV-TR and CAGE criteria for addiction to indoor tanning reported greater symptoms of anxiety and greater use of alcohol, marijuana, and other substances than those who did not meet these criteria. Depressive symptoms did not significantly vary by indoor tanning addiction status.Findings suggest that interventions to reduce skin cancer risk should address the addictive qualities of indoor tanning for a minority of individuals and the relationship of this behavior to other addictions and affective disturbance.
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    Alcohol Use Disorder Interventions Targeting Brain Sites for Both Conditioned Reward and Delayed Gratification
    (SpringerLink, 2020-01) Oberlin, Brandon G.; Shen, Yitong I.; Kareken, David A.; Psychiatry, School of Medicine
    Alcohol use disorder is a destructive compulsion characterized by chronic relapse and poor recovery outcomes. Heightened reactivity to alcohol-associated stimuli and compromised executive function are hallmarks of alcohol use disorder. Interventions targeting these two interacting domains are thought to ameliorate these altered states, but the mutual brain sites of action are yet unknown. Although interventions on alcohol cue reactivity affect reward area responses, how treatments alter brain responses when subjects exert executive effort to delay gratification is not as well-characterized. Focusing on interventions that could be developed into effective clinical treatments, we review and identify brain sites of action for these two categories of potential therapies. Using activation likelihood estimation (ALE) meta-analysis, we find that interventions on alcohol cue reactivity localize to ventral prefrontal cortex, dorsal anterior cingulate, and temporal, striatal, and thalamic regions. Interventions for increasing delayed reward preference elicit changes mostly in midline default mode network regions, including posterior cingulate, precuneus, and ventromedial prefrontal cortex-in addition to temporal and parietal regions. Anatomical co-localization of effects appears in the ventromedial prefrontal cortex, whereas effects specific to delay-of-gratification appear in the posterior cingulate and precuneus. Thus, the current available literature suggests that interventions in the domains of cue reactivity and delay discounting alter brain activity along midline default mode regions, specifically in the ventromedial prefrontal cortex for both domains, and the posterior cingulate/precuneus for delay-of-gratification. We believe that these findings could facilitate targeting and development of new interventions, and ultimately treatments of this challenging disorder.
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    Assessment of Ethanol and Nicotine Interactions in the Rat Model: Pharmacotherapeutics, Adolescence, and the Mesolimbic System
    (2019-09) Waeiss, Robert Aaron; Truitt, William A.; Hudmon, Andy; Johnson, Philip L.; McBride, William J.; Rodd, Zachary A.
    Alcohol use disorder (AUD) and nicotine dependence often result in serious health problems and are top contributors to preventable deaths worldwide. Co-addiction to alcohol and nicotine is the most common form of polysubstance abuse. Epidemiological studies indicate that more than 80% of individuals diagnosed with AUD concurrently use nicotine. The prevalence of alcohol and nicotine comorbidity may stem from interconnected mechanisms underlying these disorders. A better understanding of how these drugs interact and the biological basis behind the high comorbidity rates could generate key targets for the development of more effective treatments for AUD and nicotine dependence. The following experiments utilized four similar overall groups consisting of vehicle, ethanol (EtOH), nicotine (NIC), and EtOH+NIC. Chapter Two investigated the efficacy of naltrexone and varenicline, the pharmacological ‘gold standards’ for treating AUD and nicotine dependence, on voluntary drug intake by rats selectively bred for high EtOH drinking. The results indicated that the standard treatments for AUD and nicotine dependence were effective at reducing consumption of the targeted reinforcer but neither reduced EtOH+NIC co-use/abuse. Chapter Three examined the effects of peri-adolescent EtOH drinking on the ability of NIC infused into the posterior ventral tegmental area (pVTA) to stimulate dopamine release within the nucleus accumbens (NAc) shell during adulthood. The results suggest a cross-sensitization to NIC produced by peri-adolescent EtOH consumption demonstrated by a leftward and upward shift in the dose response curve. Chapter Four investigated the effects of intra-pVTA infusions on NAc shell neurochemistry, EtOH reward within the NAc shell, and the role of brain-derived neurotrophic factor (BDNF) on EtOH reward within that region. The data indicated that only EtOH+NIC significantly increased glutamate, dopamine, and BDNF in the NAc shell. Repeated pretreatment with EtOH+NIC also enhanced EtOH reward in the NAc shell and BDNF infusions were sufficient to recapitulate these findings. Collectively, the data indicate that concurrent exposure to EtOH and NIC results in unique neuroadaptations that promote future drug use. The failure to develop effective pharmacotherapeutics for AUD or nicotine dependence could be associated with examining potential targets in models that fail to reflect the impact of polydrug exposure.
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    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.
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    Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts
    (Springer, 2016-03) Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M.; Culverhouse, Robert C.; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M.; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N.; Maher, Brion S.; Melroy, Whitney E.; Nelson, Elliot C.; Reid, Mark W.; Robinson, Jason D.; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A.; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A.; Cannon, Dale S.; Cichon, Sven; Corley, Robin P.; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J.; Grucza, Richard A.; Hardin, Jill; Hartmann, Annette M.; Heath, Andrew C.; Herms, Stefan; Hodgkinson, Colin A.; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O.; Johnstone, Elaine; Kaneva, Radka P.; Kendler, Kenneth S.; Kiefer, Falk; Kranzler, Henry R.; Krauter, Ken S.; Levran, Orna; Lucae, Susanne; Lynskey, Michael T.; Maier, Wolfgang; Mann, Karl; Martin, Nicholas G.; Mattheisen, Manuel; Montgomery, Grant W.; Müller-Myhsok, Bertram; Murphy, Michael F.; Neale, Michael C.; Nikolov, Momchil A.; Nishita, Denise; Nöthen, Markus M.; Nurnberger, John; Partonen, Timo; Pergadia, Michele L.; Reynolds, Maureen; Ridinger, Monika; Rose, Richard J.; Rouvinen-Lagerström, Noora; Scherbaum, Norbert; Schmäl, Christine; Soyka, Michael; Stallings, Michael C.; Steffens, Michael; Treutlein, Jens; Tsuang, Ming; Wallace, Tamara L.; Wodarz, Norbert; Yuferov, Vadim; Zill, Peter; Bergen, Andrew W.; Chen, Jingchun; Cinciripini, Paul M.; Edenberg, Howard J.; Ehringer, Marissa A.; Ferrell, Robert E.; Gelernter, Joel; Goldman, David; Hewitt, John K.; Hopfer, Christian J.; Iacono, William G.; Kaprio, Jaakko; Kreek, Mary Jeanne; Kremensky, Ivo M.; Madden, Pamela A.F.; McGue, Matt; Munafò, Marcus R.; Philibert, Robert A.; Rietschel, Marcella; Roy, Alec; Rujescu, Dan; Saarikoski, Sirkku T.; Swan, Gary E.; Todorov, Alexandre A.; Vanyukov, Michael M.; Weiss, Robert B.; Bierut, Laura J.; Saccone, Nancy L.; Department of Medical & Molecular Genetics, IU School of Medicine
    The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.
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    Attacking the Drug Epidemic: Healthcare Delivery Perspective
    (2017) Oruche, Ukamaka M.
    Addiction is a chronic and recurring brain disease. Despite the associated symptoms and behaviors, prevention works, treatment is effective, and recovery is possible for everyone. Together we can attack current drug epidemic using a public health framework of integrated, comprehensive and multipronged approach appropriate to each person’s need.
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    Cortical Connectivity in Alcoholism
    (2019-09) Chumin, Evgeny Jenya; Kareken, David A.; Dzemidzic, Mario; Goñi, Joaquín; Harezlak, Jaroslaw; Lapish, Christopher C.; Yoder, Karmen K.
    Alcoholism carries significant personal and societal burdens, and yet we still lack effective treatments for alcohol use disorders. Several lines of research have demonstrated disruption of major white matter (WM) tracts in the brains of detoxified alcoholics. Additionally, there are several reports of alterations in the dopaminergic system of alcoholics. A better understanding of the relationships of brain structure and function in the alcoholic brain is necessary to move toward more efficacious pharmacological interventions. In this dissertation, there are three main chapters. First, reduced WM integrity was reported in a sample of individuals with active alcohol use disorder (AUD). This is a relatively understudied population, which is believed to represent a less severe phenotype compared to the in-treatment samples that are typically studied. Second, higher WM integrity was reported in a sample of college-age, active AUD. In a subsample of these individuals, graph theory measures of structural brain network connectivity were shown to be altered in cigarette-smoking social-drinking controls and smoking AUD subjects, compared to nonsmoking healthy individuals. Finally, a novel multimodal approach that combines diffusion weighted imaging and [11C]raclopride positron emission tomography identified differential relationships between frontostriatal connectivity and striatal dopamine tone in active AUD versus social-drinking controls. This suggests that aberrations in frontostriatal connectivity may contribute to reported differences in dopaminergic function in AUD. In summary, these results show that similar to detoxified/in-treatment alcoholics, active AUD samples present with WM integrity alterations, and changes in both structural connectivity and frontostriatal structure/function relationships.
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    Drugs of Abuse Can Entrain Circadian Rhythms
    (Hindawi Publishing Corporation, 2007-11-02) Kosobud, Ann E.K.; Gillman, Andrea G.; Leffel, Joseph K., II; Pecoraro, Norman C.; Rebec, G.V.; Timberlake, William; Neurology, School of Medicine
    Circadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse.
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    Effects of ceftriaxone on ethanol, nicotine or sucrose intake by alcohol-preferring (P) rats and its association with GLT-1 expression
    (Elsevier, 2016-06-21) Sari, Youssef; Toalston, Jamie E.; Rao, P.S.S.; Bell, Richard L.; Psychiatry, School of Medicine
    Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We have shown that administration of ceftriaxone (CEF), a β-lactam antibiotic, reduced EtOH intake and increased glutamate transporter 1 (GLT-1) expression in mesocorticolimbic regions of male and female alcohol-preferring (P) rats. In the present study, we tested whether CEF administration would reduce nicotine (NIC) and/or EtOH intake by adult female P rats. P rats were randomly assigned to 4 groups: (a) 5% sucrose (SUC) or 10% SUC [SUC], (b) 5% SUC+0.07mg/ml NIC and 10% SUC+0.14mg/ml NIC [NIC-SUC], 15% EtOH and 30% EtOH [EtOH] and (d) 15% EtOH+0.07mg/ml NIC and 30% EtOH+0.14mg/ml NIC [NIC-EtOH]. After achieving stable intakes (4weeks), the rats were administered 7 consecutive, daily i.p. injections of either saline or 200mg/kg CEF. The effects of CEF on intake were significant but differed across the reinforcers; such that ml/kg/day SUC was reduced by ∼30%, mg/kg/day NIC was reduced by ∼70% in the NIC-SUC group and ∼40% in the EtOH-NIC group, whereas g/kg/day EtOH was reduced by ∼40% in both the EtOH and EtOH-NIC group. The effects of CEF on GLT-1 expression were also studied. We found that CEF significantly increased GLT-1 expression in the prefrontal cortex and the nucleus accumbens of the NIC and NIC-EtOH rats as compared to NIC and NIC-EtOH saline-treated rats. These findings provide further support for GLT-1-associated mechanisms in EtOH and/or NIC abuse. The present results along with previous reports of CEF's efficacy in reducing cocaine self-administration in rats suggest that modulation of GLT-1 expression and/or activity is an important pharmacological target for treating polysubstance abuse and dependence.
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    The Enduring Consequences of Prenatal Opioid Exposure
    (2022-02) Grecco, Gregory Giovanni; Sheets, Patrick; Atwood, Brady; Yamamoto, Bryan; McKinzie, David; Yoder, Karmen
    The opioid crisis has resulted in an unprecedented number of neonates born with prenatal opioid exposure; however, the long-term effects of opioid exposure on offspring behavior and neurodevelopment remain relatively unknown. I developed a translational mouse model of prenatal methadone exposure (PME) that resembles the typical pattern of opioid use by pregnant women who first use oxycodone then switch to methadone maintenance pharmacotherapy, and subsequently become pregnant while maintained on methadone. PME produced substantial impairments in offspring growth, sensorimotor milestone acquisition, and activity in an open field. Furthermore, these behavioral alterations were associated with significant disruptions in the primary motor cortex (M1). Notably, layer 5 pyramidal neurons of the M1 displayed significantly increased voltage sag which is primarily mediated by HCN1 channels. Interestingly, the α2-adrenergic receptor, a known modulator of HCN1 channels, displayed significantly increased expression in the M1 of PME animals. The locomotor activity in an open field was significantly reduced following in vivo pharmacological activation of the α2-adrenergic receptor with clonidine in PME offspring suggesting this may be therapeutic target for the hyperactivity associated with prenatal exposure to opioids. Previous work has also described an association between prenatal opioid exposure and alterations in opioid reward-related behavior; however, the effect of PME on alcohol reward remains undetermined. Given the widespread accessibility and usage, alcohol represents the most likely addictive substance the growing population of opioid exposed neonates will encounter as they age. I discovered that PME disrupts conditioned preference for alcohol, enhances the locomotor stimulating effects of alcohol, and increases alcohol consumption in a sex-dependent manner. This alcohol-reward phenotype in PME offspring was associated with altered excitatory neurotransmission and disrupted cannabinoid-mediated long-term depression (CB-LTD) in the dorsolateral striatum, an important substrate involved in compulsive drug use. Further work is required to determine the specific inputs at which CB-LTD is disrupted and if restoring this form of plasticity in PME animals prevents the enhanced alcohol addiction phenotype.