Browsing by Subject "alcohol"

Now showing 1 - 8 of 8
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    1994 Minnesota State Survey: Results and Technical Report.
    (Minnesota Center for Survey Research (MCSR), 1995) Minnesota Center for Survey Research
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    2005 Minnesota State Survey--Part II: Results and Technical Report.
    (Minnesota Center for Survey Research (MCSR), 2005) Minnesota Center for Survey Research
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    Alcohol and high blood pressure
    (2009-05-06) Abanonu, Chinemerem
    Research shows that reduction in alcohol intake among heavy drinkers significantly reduces systolic and diastolic BP. This effect was seen in hypertensive and nonhypertensive subjects and also in those already taking antihypertensive medications. The findings suggest that alcohol reduction should be recommended as an important component of lifestyle modification for the prevention and treatment of hypertension among heavy drinkers.
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    Different patterns of acute and chronic alcohol activation of the mesopontine tegmentum across cell-type, sub-region, and sex
    (2024-01) Mulloy, Sarah
    Alcohol is the most widely abused illicit substance, and rates of Alcohol Use Disorder (AUD) diagnosis have been increasing over the last 10 years. Available therapies have a wide range of side-effects and low efficacy in clinical populations; therefore, the neurobiology of alcohol addiction needs to be better understood to inform more effective treatments. Substance Use Disorder (SUD) is a multi-faceted condition impacting a wide range of neural circuits, and the effects of drugs of abuse on the neurological system varies between the class of drug, history of drug use, and behavioral symptoms of various stages of the addiction cycle. Therefore, a refined understanding of alcohol’s mechanisms of action across the various stages of addiction symptomology, and how underlying biological variables such as sex contribute to alcohol mechanism would provide valuable insight into more effective strategy for treatment intervention.All drugs of abuse including alcohol modulates the dopamine neurons in the ventral tegmental area (VTA) and cause neurobiological dysregulation of the mesolimbic reward circuitry that produces addiction-related behaviors. Voluntary alcohol consumption increases endogenous acetylcholine release in the VTA and dopamine release into Nucleus Accumbens (NAc). Blocking cholinergic signaling within the VTA using cholinergic receptor antagonists reduces dopamine release in the NAc and reduces alcohol consumption, suggesting that cholinergic signaling with the VTA regulates dopamine-mediated alcohol reward processes. The only source of acetylcholine in the VTA is from the mesopontine tegmentum (MPT), which consists of two adjacent nuclei the pedunculopontine tegmentum (PPN) and laterodorsal tegmentum (LDT). The cholinergic and glutamatergic neurons of the MPT project to the VTA and modulate dopamine burst firing, and the MPT contains reward-responsive neural populations. Direct stimulation of the cholinergic and glutamatergic MPT neurons is reinforcing, and the modulation of the MPT regulates the intake and subjective reward of drugs of abuse such as nicotine, cocaine, and morphine. However, the role of the MPT on alcohol-related behaviors is understudied. Pharmacological inhibition of MPT reduces alcohol seeking in rats, and MPT lesions block the subjective reward of alcohol in a condition place preference (CPP). Therefore, the MPT is involved in alcohol-mediated reward processing, but the exact cell-type and sub-region contributions impacted by alcohol mechanisms of action are not known. Therefore, the purpose of my thesis work was to characterize the cell-type patterns of activation across acute and chronic alcohol exposure between alcohol dose, MPT sub-region, and between sex. We investigated the effect of acute and chronic ethanol administration on cholinergic and glutamatergic neuron activation in the PPN and LDT in male and female mice. We show that ethanol activates neurons of the PPN and not the LDT in male mice. Acute 4 g/kg and chronic 15 daily injections of 2 g/kg ethanol induced Fos expression in cholinergic and glutamatergic PPN neurons in male mice, whereas ethanol did not increase cholinergic and glutamatergic neuronal activation in the LDT. In contrast, acute or chronic ethanol at either dose or duration had no effect on the activation of cholinergic or glutamatergic neurons in the MPT of female mice. Female mice had higher level of activation in cholinergic neurons compared with males after saline treatment. We also found a population of co-labeled cholinergic and glutamatergic neurons in the PPN and LDT which were highly active in the saline- and ethanol-treated groups in both sexes. These findings illustrate the complex differential effects of ethanol across dose, time point, MPT subregion and sex.
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    Governing Habitual Drunkards: Guardianship, Life Insurance, and the Medico-Legal History of Compulsive Drinking in Nineteenth-Century America
    (2021-10) Korostyshevsky, David
    During the nineteenth century, the habitual drunkard became a problematic kind of person who required medical and legal attention. Growing anxieties about compulsive drinking coalesced around the terminology of habitual drunkenness, a concept that captured the sense that alcohol caused compulsion. Religious temperance reformers, many of whom were physicians, defined habitual drunkenness as an artificial appetite, a physiological condition of habituation in which the drinker lost the physical capacity for control over drinking. Non-medical actors such as civil courts and life insurers also took up the quest to define, detect, and discipline the habitual drunkard. When intoxicated heads of households neglected their families and estates, civil courts placed them under guardianship, a legal status that recognized habitual drunkenness as a form of mental incapacity. Guardianship also abridged the habitual drunkard’s property and contract rights. In a parallel vein, life insurers sought to avoid insuring habitual drunkards through medical screening and the inclusion of temperance clauses into their policy contracts. Both courts and life insurers worked to apply generalized definitions of habitual drunkenness to specific individuals before them. In both contexts, a combination of public and private actors navigated a complex combination of scientific and medical knowledge about alcohol, religious temperance ideologies about drunkenness as sin, and changing legal doctrine regarding mental capacity as they governed and disciplined compulsive drinkers. In the adjudication of guardianship cases and in life insurers’ quest to exclude drinkers, non-medical actors established habitual drunkenness as a serviceable—albeit contested, inchoate, and often ambiguous—medico-legal category.
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    Innovative Approaches to Substance Use Measurement: Questionnaires, Screening Tools, and Smartwatch Algorithms
    (2024-07) Bush, Nicholas
    Alcohol and cannabis are two of the most widely used substances in the United States and are associated with significant public health costs. Alcohol and cannabis-related health consequences have also been increasing over the past 10 to 15 years. However, despite the increased prevalence, our ability to assess and treat individuals has stagnated. This is likely due to three main reasons: 1) a limited ability to screen individuals at risk, especially in relation to co-morbid conditions like chronic pain, 2) the increased variety of available substance products (i.e., cannabis flower vs concentrates), dosages, and ways to divide such products (i.e., drinks, grams, ounces), and 3) significant barriers to accessibility of substance-related treatment. The goals of the dissertation were to develop and validate innovative methodologies to address the identified gaps in the literature. First, we developed a brief clinical screening tool to assess risk of self-medication of pain with substance use. We used an iterative process to reduce the total number of items from 104 to a 14-item and 7-item version. We found that both versions were significantly associated with self-medication behavior and substance use health risks, with minimal differences between the two versions. Second, we modified an existing behavioral economics measure to adapt to a user’s specified preferred product (e.g., dried flower) and division method (e.g., hits or grams). The modified behavioral economics measure demonstrated convergent validity and strong criterion validity compared to the original. In addition, we demonstrated significant differences associated with user preferences, such that individuals with a preference for dried flowers showed greater demand than those with a preference for concentrations. Third, we developed a novel smartwatch algorithm in an accessible framework to detect and analyzing drinking behavior. This technology provides the technological foundation for the development of accessible just-in-time alcohol use interventions. We compared the performance of a distribution-based algorithm to a traditional machine learning model in a controlled paced drinking environment. Our distributional sip detection algorithm performed similarly to our ground truth on our behavioral outcomes (i.e., sip duration, sip interval, and number of sips). It also performed significantly better than a random forest machine learning classification model. Lastly, we validated our automatic sip detection algorithm using a simulated virtual reality bar environment to allow unrestricted drinking with validated ground truth measures. We found that the algorithm had moderate-to-high classification with our ground truth measures. In conclusion, the results from these studies provide important methodological tools designed to increase the field’s ability to develop innovative and accessible methodologies. This work will also provide the support to enhance the assessment of substance use mechanisms by improving our ability to screen, adapt and develop accessible frameworks for interventions.
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    Southeast. Asian Youth and Parent Surveys about the Use of Alcohol, Tobacco, and Other Drugs: Results and Technical Report.
    (Minnesota Center for Survey Research (MCSR), 2002) Minnesota Center for Survey Research
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    Spirits in distress: Converging plasticity of ventral tegmental area (VTA) gamma amino-butyric acid (GABA) neurons evoked by chronic ethanol and stress controls anxiety symptomatology
    (2024-07) Mitten, Eric
    The ventral tegmental area (VTA) and associated signaling has been historically implicated in reward evaluation and seeking. Due to this, dysfunction of the VTA has been largely linked to substance use disorders, including alcohol use disorder (AUD). Recent evidence has also identified a role of the VTA in stress-related anxiety disorders, highlighting its diverse functional role. The majority of work in this structure has focused on dopaminergic (DA) neurons, as well as associated DA release. However, the VTA is host to a variety of neuron populations defined by neurotransmitter content, including gamma amino-butyric acid (GABA)- releasing neurons. Existing evidence positions VTA GABA neurons as potent regulators of anxiety, fear, and aversion through regulation of neighboring VTA DA neurons as well as discrete long-range projections. Lines of evidence indicate that VTA GABA neurons exhibit enhanced activity following chronic ethanol or stress exposure. Therefore, the goals of this dissertation were to further identify plasticity evoked in VTA GABA neurons in these contexts that could contribute to enhanced activity and determine the functional role of VTA GABA neuron plasticity within these disease states. Ethanol's effects in the central nervous system and the expression of AUD has been extensively linked to plasticity in GABAergic signaling, including presynaptic GABA release and postsynaptic GABAA receptors (GABAAR) and GABAB receptors (GABABR). Moreover, G- protein gated inwardly-rectifying K+ (GIRK) channels, a primary effector of GABABR signaling, also plays a critical role in the context of AUD. While it has been partially assessed, sites of GABAergic signaling plasticity evoked by chronic ethanol in VTA GABA neurons have yet to be thoroughly assessed. In Chapter 2, we utilized slice electrophysiology to identify several forms of GABAergic plasticity. Firstly, VTA GABA neurons exhibit a significant reduction in presynaptic GABA release that was dependent on the action of GABABR's, implicating plasticity in GABABR-dependent presynaptic regulation of GABA release. We surprisingly found no effect in GABAAR- dependent currents, suggesting that postsynaptic GABAAR signaling may be largely unaffected. On the other hand, postsynaptic GABABR/GIRK-dependent currents were significantly diminished, which was found to be associated with increased intracellular localization of the GABABR1 subunit as well as GIRK2. Utilizing a constitutive knockout approach as well as VTA GABA specific CRISPR/Cas9 mediated ablation, we identified GIRK3 as necessary for this plasticity in postsynaptic GABABR/GIRK signaling. These data, in conjunction with existing evidence, suggest that GABAergic signaling plasticity in VTA GABA neurons following chronic ethanol exposure could contribute to the expression of symptoms associated with AUD. Utilizing VTA GABA specific CRISPR/Cas9 mediated ablation of GIRK2, we found that loss of GABABR/GIRK currents was sufficient to induce anxiety symptomatology, suggesting a role of VTA GABA neurons in ethanol withdrawal-induced anxiety. Stress has been demonstrated to increase the activity of VTA GABA neurons, as well as evoke plasticity that suggests VTA GABA neurons exhibit enhanced excitability. Interestingly, enhanced activity of VTA GABA neurons is required for restraint stress-induced anhedonia, suggesting a role of VTA GABA neurons in other stress-induced affective symptoms. In Chapter 3, we utilized an unpredictable footshock (uFS) protocol to assess the effect of stress on VTA GABA neurons due to its ability to reliably evoke anxiety symptomatology. uFS was sufficient to enhance the excitability of VTA GABA neurons, as assessed via increased baseline firing, increased input resistance, and decreased rheobase. Furthermore, this hyperexcitability was associated with enhanced presynaptic glutamate release, as well as diminished postsynaptic GABAAR and GABABR signaling, suggesting that stress evokes several mechanisms of intrinsic and extrinsic plasticity of VTA GABA neurons. Utilizing a chemogenetic approach, we found that enhanced excitability of VTA GABA neurons in behaviorally-naïve mice was sufficient to evoke anxiety, while diminishing excitability of VTA GABA neurons was sufficient to block the expression of uFS-induced anxiety. These data posit that VTA GABA neuron excitability is necessary for stress-induced affective symptomatology, suggesting that VTA GABA neuron dysfunction may underlie disorders associated with this symptomatology. Altogether, this work contributes to a growing body of evidence identifying the functional role of VTA GABA neurons, as well as provides insights into novel therapeutic targets for the treatment of anxiety in the context of AUD and stress-related anxiety disorders. Furthermore, this work positions VTA GABA neurons as an overlapping site of plasticity between chronic ethanol and stress that could contribute to reciprocal exacerbation of each disease state.