Problem alcohol drinking remains a major cost and burden for society. Also, rates of problem drinking in women have dramatically increased in recent decades, and women are at risk for more alcohol problems and comorbidities. The purpose of this commentary is to discuss the potential utility of cardiac measures, including heart rate (HR) and HR variability (HRV), as markers of individual and sex differences in the drive to drink alcohol.
View Article and Find Full Text PDFAlcohol use disorder extracts substantial personal, social and clinical costs, and continued intake despite negative consequences (compulsion-like consumption) can contribute strongly. Here we discuss lickometry, a simple method where lick times are determined across a session, while analysis across many aspects of licking can offer important insights into underlying psychological and action strategies, including their brain mechanisms. We first describe studies implicating anterior insula (AIC) and dorsal medial prefrontal cortex (dMPF) in compulsion-like responding for alcohol, then review work suggesting that AIC/ventral frontal cortex versus dMPF regulate different aspects of behavior (oral control and overall response strategy, versus moment-to-moment action organization).
View Article and Find Full Text PDFProblem alcohol drinking continues to be a substantial cost and burden. In addition, alcohol consumption in women has increased in recent decades, and women can have greater alcohol problems and comorbidities. Thus, there is a significant need for novel therapeutics to enhance sex-specific, individualized treatment.
View Article and Find Full Text PDFExcessive intake plays a significant role in the development of alcohol use disorder and impacts 15 million Americans annually, with approximately 88 000 dying from alcohol related deaths. Several facets we contribute to alcohol use disorder include impulsivity, motivation, and attention. Previous studies have used the 5-Choice Serial Reaction Time Task (5-Choice) to analyze these types of behaviors using sugar, but recently we have published using 10% alcohol as the reward.
View Article and Find Full Text PDFMuch remains unknown about the etiology of compulsion-like alcohol drinking, where consumption persists despite adverse consequences. The role of the anterior insula (AIC) in emotion, motivation, and interoception makes this brain region a likely candidate to drive challenge-resistant behavior, including compulsive drinking. Indeed, subcortical projections from the AIC promote compulsion-like intake in rats and are recruited in heavy-drinking humans during compulsion for alcohol, highlighting the importance of and need for more information about AIC activity patterns that support aversion-resistant responding.
View Article and Find Full Text PDFUncontrollable binge drinking is becoming an increasingly prevalent issue in our society. This is a factor that plays a role in the development of alcohol use disorder (AUD). AUD impacts 15 million Americans annually, with approximately 88,000 dying from alcohol related deaths.
View Article and Find Full Text PDFIntroduction: Mental health conditions remain a substantial and costly challenge to society, especially in women since they have nearly twice the prevalence of anxiety disorders. However, critical mechanisms underlying sex differences remain incompletely understood. Measures of cardiac function, including heart rate (HR) and HR variability (HRV), reflect balance between sympathetic (SNS) and parasympathetic (PNS) systems and are potential biomarkers for pathological states.
View Article and Find Full Text PDFAlcohol use disorder (AUD) is related to excessive binge alcohol consumption, and there is considerable interest in associated factors that promote intake. AUD has many behavioral facets that enhance inflexibility toward alcohol consumption, including impulsivity, motivation, and attention. Thus, it is important to understand how these factors might promote responding for alcohol and can change after protracted alcohol intake.
View Article and Find Full Text PDFAlcohol use disorder (AUD) is characterized as a chronic, relapsing disease with a pattern of excessive drinking despite negative consequences to an individual's life. Severe chronic alcohol use impairs the function of the medial prefrontal cortex (mPFC), which contributes to alcohol-induced cognitive and executive dysfunction. The mPFC contains more mitochondria compared to other cortical areas, which suggests mitochondrial damage may occur in AUD and trigger subsequent behavior change.
View Article and Find Full Text PDFKynurenic acid (KYNA), a glial-derived metabolite of tryptophan metabolism, is an antagonist of the alpha 7 nicotinic acetylcholine receptor and the glycine-binding site of -methyl-d-aspartate (NMDA) receptors. Kynurenic acid levels are increased in both the brain and cerebrospinal fluid of several psychiatric disorders including bipolar disorder, schizophrenia, and Alzheimer disease. In addition, pro-inflammatory cytokines have been found to be elevated in the blood of schizophrenic patients suggesting inflammation may play a role in psychiatric illness.
View Article and Find Full Text PDFChronic binge alcohol drinking is known to increase risky decision through pathological impulsive behaviors. Recently, we established a novel rodent model of ethanol-induced waiting impulsivity using 5-choice serial reaction time task (5-CSRTT) in mice. However, molecular mechanisms underlying the chronic binge ethanol-induced waiting impulsivity is not well characterized.
View Article and Find Full Text PDFImpulsivity is defined as a predisposition toward rapid, unplanned reactions in response to internal or external stimuli, often yielding negative consequences. Accordingly, impulsivity is considered a significant risk factor for developing addictive behaviors. The hippocampus is involved in regulating behavioral adaptability and learned behaviors.
View Article and Find Full Text PDFWaiting impulsivity is a risk factor for many psychiatric disorders including alcohol use disorder (AUD). Highly impulsive individuals are vulnerable to alcohol abuse. However, it is not well understood whether chronic alcohol use increases the propensity for impulsive behavior.
View Article and Find Full Text PDFA correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
View Article and Find Full Text PDFOligodendrocytes are essential regulators of axonal energy homeostasis and electrical conduction and emerging target cells for restoration of neurological function. Here we investigate the role of protease activated receptor 2 (PAR2), a unique protease activated G protein-coupled receptor, in myelin development and repair using the spinal cord as a model. Results demonstrate that genetic deletion of PAR2 accelerates myelin production, including higher proteolipid protein (PLP) levels in the spinal cord at birth and higher levels of myelin basic protein and thickened myelin sheaths in adulthood.
View Article and Find Full Text PDFThe random nature of seizures poses difficult challenges for epilepsy research. There is great need for a reliable method to control the pathway to seizure onset, which would allow investigation of the mechanisms of ictogenesis and optimization of treatments. Our hypothesis is that increased random afferent synaptic activity (i.
View Article and Find Full Text PDFThe neural circuit of the dorsal hippocampus (dHip) and nucleus accumbens (NAc) contributes to cue-induced learning and addictive behaviors, as demonstrated by the escalation of ethanol-seeking behaviors observed following deletion of the adenosine equilibrative nucleoside transporter 1 (ENT1) in mice. Here we perform quantitative LC-MS/MS neuroproteomics in the dHip and NAc of ENT1 mice. Using Ingenuity Pathway Analysis, we identified proteins associated with increased long-term potentiation, ARP2/3-mediated actin cytoskeleton signaling and protein expression patterns suggesting deficits in glutamate degradation, GABAergic signaling, as well as significant changes in bioenergetics and energy homeostasis (oxidative phosphorylation, TCA cycle, and glycolysis).
View Article and Find Full Text PDFInduced pluripotent stem cells (iPSCs) show considerable promise for cell replacement therapies for Huntington's disease (HD). Our laboratory has demonstrated that tail-tip fibroblasts, reprogrammed into iPSCs via two adenoviruses, can survive and differentiate into neuronal lineages following transplantation into healthy adult rats. However, the ability of these cells to survive, differentiate, and restore function in a damaged brain is unknown.
View Article and Find Full Text PDFInduced pluripotent stem cells (iPSCs) offer certain advantages over embryonic stem cells in cell replacement therapy for a variety of neurological disorders. However, reliable procedures, whereby transplanted iPSCs can survive and differentiate into functional neurons, without forming tumors, have yet to be devised. Currently, retroviral or lentiviral reprogramming methods are often used to reprogram somatic cells.
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