Browsing by Subject "Substance-Related Disorders"
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Item An American (nose) trilogy: illicit drug and substance abuse; cocaine, phencyclidine, amphetamine-like nasal inhalers(1981-05-07) Anderson, Ron J.This Internal Medicine Grand Rounds protocol is comprised of three sections that follow the title page and the dedication and acknowledgements page. Each section has its own bibliography. All three sections were presented on the same date. Page numbers correspond to the digital page number displayed in the file.Item Benzodiazepine dependence and withdrawal(1988-09-01) Reed, William GaryItem The cardiovascular complications of cocaine use(1990-06-28) Lange, Richard A.Item Delivery Continuity and Neonatal Disposition to Birthing Parent in Individuals with Substance Use Disorder at Parkland Health(2024-01-30) Afsari, Macy; White, Alesha; Morillos, Stephanie; Fisher, Amber; McNeil, Jessica; Faucher, Mary Ann; Cordova, Polly; Onisko, Nancy S.; Andino, Aldo; Kern, Joshua; Kleinschmidt, Kurt; McIntire, Donald D.; Adhikari, Emily H.OBJECTIVE: Infants born to individuals with substance use disorder (SUD) are at increased risk of removal from their parent. Individuals with SUD in pregnancy receive obstetric care by a multidisciplinary care team (MCT) at our safety-net hospital. We evaluated factors associated with delivery continuity and neonatal discharge to birthing parent among patients with SUD. STUDY DESIGN: This is a retrospective cohort study of pregnant patients with SUD who accessed Parkland Health (PHHS) between July 28, 2021 and June 25, 2022. We compared MCT interactions among patients who did and did not deliver at PHHS as well as neonatal disposition and outcomes for infants born to individuals with SUD and with specifically opioid use disorder (OUD). RESULTS: Among 256 pregnant individuals with SUD who accessed care in our system, 144 (56%) received care by our MCT during pregnancy or at the delivery hospitalization. 98 of these patients delivered at PHHS and 46 delivered elsewhere (68% vs 32%, p<0.001). Significantly more eligible individuals who delivered at PHHS accepted medication-assisted treatment (MAT) compared to those who did not (88% vs 70%, p=0.025). Of 139 patients with SUD who delivered at PHHS, 91 (65%) infants were discharged home with the birthing parent. Parents who went home with their infants were more likely to use cannabis (33% vs 4%, p<0.001) and less likely to use opioids (34% vs 63%, p=0.003). They attended more prenatal visits (median [IQR] 9 [5,11] vs 1 [0,4], p<0.001) and met less frequently with our multidisciplinary team providing integrated SUD treatment (1 [0,10] vs 4 [1, 14.5], p=0.026). Neonates discharged with the birthing parent were less likely to have a positive meconium (7% vs 75%, p<0.001) or urine toxicology (2% vs 67%, p<0.001) and were less likely to have a 5-minute Apgar <4 (0% vs 4%, p=0.04). Of 62 patients with OUD, 31 (50%) were discharged with their neonate. Those who used opioids alone were more likely than individuals with opioid-polysubstance misuse to retain charge of their infant (78% vs 43%, p=0.018). CONCLUSION: Increased interactions and MAT with a team specializing in care of pregnant patients with SUD is associated with delivery continuity. Neonatal disposition and outcomes are influenced more by maternal drug of choice and prenatal care attendance than by MCT interactions because of variance in SUD complexity. Opioid-polysubstance misuse is associated with separation of maternal infant dyad.Item Emergency management of drug overdose(1990-07-26) Reed, William GaryItem Epigenetic Mechanisms in Drug Addiction(2010-11-02) Renthal, William Russell; Nestler, Eric J.Changes in gene expression in brain reward regions are thought to contribute to the pathogenesis and persistence of drug addiction. Recent studies have begun to focus on the molecular mechanisms by which drugs of abuse, and related environmental stimuli, such as drug-associated associated cues or stress, converge on the genome to alter specific geneprograms. Increasing evidence suggests that these stable gene expression changes in neurons are mediatedin part by epigenetic mechanisms that alter chromatin structure on specific gene promoters. Indeed, genome-wide analysis using chromatin immunoprecipitation coupled with promoter microarrays in vivo, identified on which genes chronic cocaine exposure alters histone acetylation and methylation in the nucleus accumbens, a key brain reward region. In addition to providing novel insight into basic transcriptional mechanisms co-opted by cocaine, these data revealed a new class of cocaine-regulated genes, the sirtuins, which potently regulate reward behavior. In order to further understand the mechanisms by which cocaine regulates chromatin structure, I investigated enzymes which control levels of histone acetylation, histone deacetylases (HDACs). Chronic, but not acute, exposure to cocaine decreased the function of a class II HDAC, HDAC5, in the NAc, which allows for increased histone acetylation and transcription of HDAC5 target genes. This regulation is behaviorally important, as loss of HDAC5 causes hypersensitive responses to chronic, but not acute, cocaine. I have also identified a key roleof the class I HDAC, HDAC1, which interacts with the drug-induced transcription factor, ΔFosB, to repress c-fos gene induction in striatum after chronic psychostimulant exposure. Taken together, these findings suggest that proper balance of histone acetylation in the NAc is a crucial factor in the saliency of cocaine action, and that disruption of this balance may be involved in the transition from acuteadaptive responses to chronic psychiatric illness.Item Long-Term Efficacy of a Therapeutic Community Program for the Homeless: Personality, Substance Abuse, and Social Support Factors That Affect Outcome(2006-12-19) Houghteling, Lisa Nicole; Herman, JohnHomelessness is a social problem that is multidetermined and requires complex and comprehensive solutions. The issues of homelessness are heterogeneous in nature, with a multitude of complex problems encumbering this diverse population. The high incidence of co-occurring mental illness and substance abuse compound the already harsh consequences of homelessness and often exacerbate the extreme disaffiliation from others experienced by these individuals. Many attempts have been made to remedy this problem, often by addressing each of the issues of homelessness separately. However, there exists a consensus among researchers that this problem must be addressed from a multidimensional treatment approach in order to effectively bring about lasting change. The Therapeutic Community Program at Austin Street Centre in Dallas, Texas is an approach that has combined several treatment modalities into one comprehensive program addressing a variety of issues simultaneously. Group therapy is the cornerstone of this approach, whereby individuals work out their interpersonal difficulties and gain a sense of community and belonging while addressing the issues of mental illness and substance abuse. Previous research on the effectiveness of this Therapeutic Community Program has been promising, albeit preliminary. Despite a high attrition rate, participants demonstrated significant improvements with regard to substance abuse, psychological distress, occupational performance, and interpersonal functioning compared to a group of controls who did not participate in the program. The current study aimed to further these results by demonstrating similar gains in terms of social and psychological functioning, as well as, provide a preliminary investigation into factors that affect program attrition and outcome. A group of 75 therapeutic community program participants at Austin Street were compared to a group of 30 controls who utilized only the basic overnight shelter services offered. As in the previous study, the therapeutic community program was found to be an effective means to a positive outcome. Program participants remained in the therapeutic community for longer and were more likely to experience a positive outcome than controls. Significantly fewer program participants evidenced signs of substance dependence at 3 month follow-up than at intake. Those program participants who evidenced less substance abuse at 3 months were more likely to experience a positive outcome. Additionally, these individuals were shown to have fewer problems relating interpersonally and fewer psychiatric symptoms at baseline than those who continued to abuse substances. Program participants also demonstrated a steady decrease in psychiatric symptoms, symptom distress, problems relating interpersonally, and problems in their social role.Item [News](1989-02-01) Harrell, AnnItem [News](1985-02-19) Johnson, Kevin OrlinItem Regulation of Circadian Genes by Cocaine in Striatal Regions and Their Role in Drug Reward(2012-07-10) Falcón-Morales, Edgardo; McClung, Colleen A.Disruptions in circadian rhythms are associated with neuropsychiatric disorders, including drug addiction. Indeed, mounting evidence reveals a role for the circadian clock in the regulation of drug reward and reward-related behaviors. Conversely, drugs of abuse are known to dysregulate circadian-associated processes and entrain locomotor behavior. The circadian clock is governed by a master pacemaker in the Suprachiasmatic Nucleus(SCN) of the anterior hypothalamus. However, the components of this circadian clock machinery are expressed throughout the brain and body, allowing for the occurrence of SCN-dependent or independent peripheral oscillators. One such brain circuit in which circadian genes are expressed is the mesolimbic dopaminergic pathway, containing brain regions such as the Nucleus Accumbens(NAc) and the Caudate Putamen (CP), among others. We set out to investigate how repeated cocaine exposure regulates core clock circadian genes in striatal regions and conversely, how core clock circadian genes regulate cocaine’s rewarding effects. Additionally, the potential regulation of rhythmic dopamine receptor expression directly by clock components and how their rhythmic expression is altered by repeated cocaine exposure was assessed. Chapter 3 determined circadian gene regulation in both the NAc and CP by cocaine. Not only did chronic cocaine upregulated a number of circadian genes at a specific timepoint, like Npas2 and the Per genes, but also altered or disrupted 24-hr rhythmic expression of these genes. Chapter 4 investigated the role of core circadian clock genes in cocaine reward, as measured by conditioned place preference. Npas2 mutant mice exhibited a decreased preference for cocaine, an effect that was recapitulated by viral-mediated Npas2 knockdown specifically in the NAc. Per mutant mice displayed an increase in cocaine preference. Knockdown of mPer1 and mPer2 in the NAc led to a trend towards increased preference. Chapter 5 identified a potential role for NPAS2 in the regulation of dopamine receptor rhythmic expression in the NAc, and that chronic cocaine disrupts this rhythmicity. These findings suggest an important role for Npas2 as mediator of cocaine responses in the NAc. Moreover, they further elucidate the bidirectional interactions between the circadian and reward systems, implicating the circadian control of the dopaminergic system in this interplay.Item The Role of DNA Methylation in Addiction and Depression(2010-11-02) LaPlant, Quincey Charles; Nestler, Eric J.Despite abundant expression of DNA methyltransferases (Dnmt’s) in brain, the regulation and behavioral role of DNA methylation remain poorlyunderstood. I found that Dnmt3a expression is persistently regulated in nucleus accumbens (NAc),a key brain reward region, by chronic cocaine or chronic social defeat stress. Moreover, NAc specific manipulations that block DNA methylation potentiate cocaine reward and exert antidepressant-like effects, whereas NAc specific Dnmt3a overexpression attenuates cocaine reward and is pro-depressant. On a cellular level, I discovered that chronic cocaine selectively increases thin dendritic spines on NAc neurons and that DNA methylation is both necessary and sufficient to mediate these effects. I then used complementary genome wide techniques aimed at identifying cocaine-induced DNA methylation at gene targets. Transcriptional profiling experiments in which I virally overexpressed Dnmt3a or pharmacologically blocked DNA methylation identified an important role of DNA methylation in regulating the mRNA expression of a number of immediate early genes—several of which are known to regulate dendritic spine morphology. Taken together, these data establish the importance of Dnmt3a in the NAc in regulating molecular, cellular, and behavioral plasticity to emotional stimuli.Item The Role of Incarceration in Treatment-Seeking Veterans with PTSD: Evaluating Differences in Trauma Symptoms, Suicidality, and Substance Use(August 2021) Sligar, Kylie Blake; LePage, James; Jeon-Slaughter, Haekyung; Shivakumar, Geetha; Pai, Anushka; Smith, JuliaVeterans are an at-risk population with increased chances of exposure to trauma, mental health diagnoses, substance use, and suicidality. Individuals who have been incarcerated demonstrate similar increased risks. As such, when a Veteran also has a history of incarceration, these risks may be exacerbated. It is posited the rate of PTSD among Veterans is 11-20% (National Center of PTSD, 2019). Additionally, it is estimated over 120,000 Veterans are currently incarcerated, with as many as 67% having a mental illness or substance use disorder (Finlay et al., 2017; Bronson et al., 2015). This study aimed to examine how a history of incarceration may impact trauma symptoms in Veterans, and how this differs when compared to Veterans without an incarceration history. The data did not support overall differences between these two groups; however, exploratory analyses suggest potential areas of future directions. Exploratory analyses suggest potential differences in PTSD symptomology, specifically increased endorsement of Cluster C / avoidance among Veterans with PTSD, and increased risk taking among Veterans with PTSD and an incarceration history. Results also suggested higher rates of substance use treatment among Veterans with PTSD and an incarceration history. Lastly, analyses suggest higher endorsement of feeling "tense and keyed up" among Veterans with PTSD. No differences were found between groups in areas of PTSD severity, number of endorsed trauma events, suicidality, or adverse childhood events.Item The Role of Lateral Hypothalamic Neuropeptides in Drug Addiction and Feeding Behavior(2004-08-19) Georgescu, Dan; DiLeone, Ralph J.; Nestler, Eric J.; Bibb, James A.; Yanagisawa, MasashiA major goal of both feeding and drug abuse research is to understand the neural and molecular mechanisms that control intake and how dysfunction of these systems can lead to excessive food ingestion or addiction. Numerous studies have found synergistic effects of drugs of abuse and metabolism on reward related behaviors such as lateral hypothalamus self-stimulation (LHSS). The lateral hypothalamus (LH) is a brain structure with prominent roles in feeding, arousal and reward. Recent studies have found that melanin concentrating hormone (MCH), orexin A and orexin B are exclusively expressed in this brain area, opening the possibility that these LH neuropeptides could be involved in feeding behavior and drug addiction. This study shows that orexin neurons, and not the nearby LH neurons expressing MCH have 歯pioid receptors and respond with induction of cFos and CRE- mediated transcription to chronic morphine administration and opiate antagonist-precipitated morphine withdrawal. Additionally, orexin knockout mice and C57BL/6J mice that received a selective OX1R antagonist develop attenuated morphine dependence, as indicated by a less severe antagonistprecipitated withdrawal syndrome. These findings support a role for the orexin system in molecular adaptations to morphine, and demonstrate dramatic differences in molecular responses among different populations of LH neurons. This study also establishes a role for MCH and its receptor (MCH1R) in mediating a hypothalamic- limbic circuit that regulates feeding and related behaviors. Particularly intriguing was the high density of MCH1R in nucleus accumbens shell (AcSh), a region important in the regulation of appetitive behavior. Direct delivery of an MCH1R receptor antagonist to the AcSh blocked feeding and produced an antidepressant- like effect in the forced swim test, while intra-AcSh injection of MCH had opposite effects. Expression and biochemical studies demonstrated that MCH is modulating feeding behavior by interacting with the dopamine and glutamate pathways in the enkephalin and dynorphin positive neurons of AcSh. This work identifies a novel hypothalamic-AcSh circuit that may integrate the homeostatic and hedonic aspects of feeding. Together, these studies identify new roles for LH peptides in drug addiction, feeding and depression and help to define novel molecular mechanisms and neural circuits controlling complex behavior.Item [Southwestern News](2003-01-02) Harrell, AnnItem [Southwestern News](2001-02-12) Echeverria, Ione; Harrell, AnnItem [Southwestern News](2002-09-11) Harrell, AnnItem [Southwestern News](2002-09-23) Harrell, AnnItem [Southwestern News](2005-10-21) Hansard, Donna StephItem [Southwestern News](2005-06-13) Hansard, Donna StephItem [Southwestern News](1994-08-12) Martinez, Emily