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News Article | May 4, 2017
Site: www.winespectator.com

Just like your brain after a night of excessive drinking, the science behind hangovers is a little fuzzy Many of us like to believe we're well past our days of waking up feeling a bit wooly, but the fact is, hangovers can happen to the best of us—and to add injury to insult, they get worse with age. So if you had too much bubbly at a party, or one glass more of Merlot proved to be one glass too many, what do you do to combat the headache, nausea, fatigue and shakiness that might afflict you the following day? For ancient Romans, the "best" way to recover after a wild bacchanal was to eat fried canary for breakfast. According to Irish legend, burying yourself in wet river sand will ease your head after too many pints. Medieval European overindulgers believed consuming raw eel could counteract the effects of too much booze-driven merriment. You may scoff at these remedies, but how much better are our modern-day day-after rituals? There's not a lot of science-backed information about hangovers—we still don't even know why we get them. And if we can't pinpoint the cause, how can we expect to have a cure? "Nobody knows what causes it," Jonathan Howland, professor at Boston University and director of the injury prevention center at Boston Medical Center told Wine Spectator. "So to say that you're going to cure a hangover, or prevent a hangover, or you're just going to magically take care of all the symptoms, well, that's maybe stretching it a bit." But don't lose hope. Just because there's no proven end-all be-all antidote for your post-wine woes, there are still some proven methods for feeling better. "There are various things that can treat symptoms of hangover that are perfectly legitimate," Howland said. Water is at the top of the list for anyone looking to treat a hangover. "Lots of water, and my personal favorite, coconut water—loaded with electrolytes—can help the issue of dehydration and really make us feel better," said registered dietician Isabel Smith via email. But while rehydrating is important, especially after a long night of alcohol, studies suggest that dehydration is just one reason we feel so bad after drinking too much. Hangovers are caused by different reactions as our bodies process alcohol—a lot of the effects we feel while hungover are due to dehydration, but even if we are hydrated, there are plenty of other factors. So while you absolutely should drink lots of water after a night on the town, don't expect to make a miraculous recovery because of it. OK, so what about the harder stuff? "Does the hair of the dog work? It does, actually, but that is probably the worst possible thing you can do," said Thomas Kash, associate professor at the University of North Carolina Bowles Center for Alcohol Studies. It's well-known that a bloody mary at brunch might make you feel better temporarily, dulling the pain, but it's only prolonging the inevitable, and could leave you with a worse hangover than the one you were trying to get rid of. Kash and his fellow researchers also stress that a prolonged pattern of drinking to avoid hangovers can lead to dangerous habits. If you can't imbibe away your hangover pain, what about eating? Many hungover folks indulge in fatty foods, believing it soaks up the alcohol. Unfortunately, research suggests this is a myth. According to the Alcohol Hangover Research Group, a coalition of international researchers, hangovers develop as your blood-alcohol concentration is dropping. So if you're hungover, there's not really any alcohol present in the stomach for the food to soak up. So why do people think this method helps? "It could be that they were just hungry," Kash said. "They have a headache, they're tired, they feel kind of sick, but they're hungry on top of it." According to Damaris Rohsenow, associate director of the Center for Alcohol and Addiction Studies at Brown University, many researchers cite inflammation, brought on by different factors like the presence of congeners in the alcohol you drink or the release of chemicals in the body called cytokines, as a key cause of hangovers. So if you pop anti-inflammatory painkillers when you have a raging hangover headache, you may be getting straight to the source of the matter. But remember, not all over-the-counter painkillers are created equally. Acetaminophen, for example, is processed in the liver, so taking it after overdoing alcohol can cause serious damage. Aspirin and ibuprofen are considered safer, but you should never exceed the recommended dosage, since there is still a small risk of damaging the stomach lining. And wait until the morning after to take them—if you take them before bed after a night of drinking, not only is there a higher risk of damage (since there's still alcohol in your system), but it's also likely you'll still be asleep when the painkillers reach their peak effectiveness. What about those miracle pills advertised? Quick-fix products like Blowfish—an FDA-approved tablet that claims to "make you feel like a human again" with its formula of aspirin and caffeine—have made headlines in recent years. But just like all of the aforementioned tactics, researchers insist that these "cures" will only address a few symptoms, and each person will respond to them differently. While science may not have a silver bullet for hangovers, that hasn't stopped people from selling remedies. And there may be partial merit to some of them. A new trend in hangover treatment has been popping up in party cities like Las Vegas, Miami, New York and London: Intravenous hydration therapy. "Doctors, nurses, firefighters, people in the military have been using IV therapy long before it's been available to the general public," said Johnny Parvani, emergency-room physician and CEO of Reviv, a medical spa that provides non-emergency IV treatments. Not only does IV therapy help you rehydrate, but it could also directly address another possible cause for hangovers. "Ultimately, alcohol is converted into carbon dioxide and water, but the intermediaries between the alcohol and the final end product are some toxic metabolites," said Parvani. "Fluids are the most effective way of flushing all of these things out." It could put a spring back in your step—if you're willing to shell out between $99 to $300. Those who prefer to "sweat it out" with exercise (and elicit eye-rolls from their less athletically inclined peers) are encouraged to do so, but with caution. "Sweating a little bit sometimes can make you feel better," said New York–based wellness coach Danielle Pashko. "Through sweat you excrete toxins. But I wouldn't tell somebody to go for a run if they're not feeling up to it. If you're not feeling well, you could do a leisurely walk or something easy." And if you do choose to exercise, make sure you're drinking a lot of water to stay hydrated. "I think there's probably not a miracle cure out there," Kash said. And there may never be, he adds, since medical research tends to focus on more pressing matters than your aching head after a night of Prosecco. "People are more concerned with binge drinking and heavy alcohol dependency." Unfortunately for our Sunday morning selves, there doesn't seem to be a real hangover "cure" out there, just different ways to cope with the symptoms. So if you want to stay indoors all day and order pizza, go for it. If you'd rather pump vitamins into your bloodstream and then run a few miles, more power to you. As long as you stay hydrated and listen to your body—and remember that the only real way to avoid a hangover is to drink in moderation—do what feels best for you. It should only last a few hours, anyway.


Bohnsack J.P.,University of North Carolina at Chapel Hill | Carlson S.L.,University of North Carolina at Chapel Hill | Morrow A.L.,University of North Carolina at Chapel Hill | Morrow A.L.,Bowles Center for Alcohol Studies
Neuropharmacology | Year: 2016

The GABAA α4 subunit exists in two distinct populations of GABAA receptors. Synaptic GABAA α4 receptors are localized at the synapse and mediate phasic inhibitory neurotransmission, while extrasynaptic GABAA receptors are located outside of the synapse and mediate tonic inhibitory transmission. These receptors have distinct pharmacological and biophysical properties that contribute to interest in how these different subtypes are regulated under physiological and pathological states. We utilized subcellular fractionation procedures to separate these populations of receptors in order to investigate their regulation by protein kinases in cortical cultured neurons. Protein kinase A (PKA) activation decreases synaptic α4 expression while protein kinase C (PKC) activation increases α4 subunit expression, and these effects are associated with increased β3 S408/409 or γ2 S327 phosphorylation respectively. In contrast, PKA activation increases extrasynaptic α4 and δ subunit expression, while PKC activation has no effect. Our findings suggest synaptic and extrasynaptic GABAA α4 subunit expression can be modulated by PKA to inform the development of more specific therapeutics for neurological diseases that involve deficits in GABAergic transmission. © 2016 Elsevier Ltd. All rights reserved.


Sparta D.R.,University of North Carolina at Chapel Hill | Sparta D.R.,Bowles Center for Alcohol Studies | Hovelso N.,University of North Carolina at Chapel Hill | Hovelso N.,Lundbeck | And 7 more authors.
Journal of Neuroscience | Year: 2014

Forming and breaking associations between emotionally salient environmental stimuli and rewarding or aversive outcomes is an essential component of learned adaptive behavior. Importantly, when cue-reward contingencies degrade, animals must exhibit behavioral flexibility to extinguish prior learned associations. Understanding the specific neural circuit mechanisms that operate during the formation and extinction of conditioned behaviors is critical because dysregulation of these neural processes is hypothesized to underlie many of the maladaptive and pathological behaviors observed in various neuropsychiatric disorders in humans. The medial prefrontal cortex (mPFC) participates in the behavioral adaptations seen in both appetitive and aversive-cue-mediated responding, but the precise cell types and circuit mechanisms sufficient for driving these complex behavioral states remain largely unspecified. Here, we recorded and manipulated the activity of parvalbumin-positive fast spiking interneurons (PV+FSIs) in the prelimbic area (PrL) of the mPFC in mice. In vivo photostimulation of PV+FSIs resulted in a net inhibition of PrL neurons, providing a circuit blueprint for behavioral manipulations. Photostimulation of mPFC PV+ cells did not alter anticipatory or consummatory licking behavior during reinforced training sessions. However, optical activation of these inhibitory interneurons to cues associated with reward significantly accelerated the extinction of behavior during non-reinforced test sessions. These data suggest that suppression of excitatory mPFC networks via increased activity of PV+FSIs may enhance reward-related behavioral flexibility. © 2014 the authors.


Crowley S.K.,University of North Carolina at Chapel Hill | O'Buckley T.K.,Bowles Center for Alcohol Studies | Schiller C.E.,University of North Carolina at Chapel Hill | Morrow A.L.,University of North Carolina at Chapel Hill | And 2 more authors.
Psychopharmacology | Year: 2016

Rationale: Anxiety during pregnancy has been linked to adverse maternal health outcomes, including postpartum depression (PPD). However, there has been limited study of biological mechanisms underlying behavioral predictors of PPD during pregnancy. Objectives: Considering the shared etiology of chronic stress amongst antenatal behavioral predictors, the primary goal of this pilot study was to examine associations among stress-related physiological factors (including GABA-ergic neurosteroids) and stress-related behavioral indices of anxiety during pregnancy. Methods: Fourteen nulliparous women in their second trimester of a singleton pregnancy underwent speech and mental arithmetic stress, following a 2-week subjective and objective recording of sleep-wake behavior. Results: Lower cortisol, progesterone, and a combined measure of ALLO + pregnanolone throughout the entire stressor protocol (area under the curve, AUC) were associated with greater negative emotional responses to stress, and lower cortisol AUC was associated with worse sleep quality. Lower adrenocorticotropic hormone was associated with greater anxious and depressive symptoms. Stress produced paradoxical reductions in cortisol, progesterone, and a combined measure of allopregnanolone + pregnanolone, while tetrahydrodeoxycorticosterone levels were elevated. Conclusions: These data suggest that cortisol, progesterone, and ALLO + pregnanolone levels in the second trimester of pregnancy are inversely related to negative emotional symptoms, and the negative impact of acute stress challenge appears to exert its effects by reducing these steroids to further promote negative emotional responses. © 2016 Springer-Verlag Berlin Heidelberg.


Berger L.,University of Wisconsin - Milwaukee | Brondino M.,University of Wisconsin - Milwaukee | Gwyther R.,Bowles Center for Alcohol Studies | Garbutt J.C.,Bowles Center for Alcohol Studies | Garbutt J.C.,University of North Carolina at Chapel Hill
Journal of the American Board of Family Medicine | Year: 2016

Background: In a recent study conducted in a family medicine setting, the medication acamprosate was found not to be efficacious in the treatment of alcohol dependence, but a drinking goal of abstinence was found to have positive effects on alcohol use outcomes. The purpose of this secondary analysis was to further understand which patients with an alcohol use disorder may be most successfully treated in a primary care setting. Methods: The study was exploratory and used a trajectory-based approach based on data from the acamprosate treatment trial of 100 participants (recruited mostly by advertisement) who were randomly assigned to receive either acamprosate or a matching placebo. Post hoc trajectories of alcohol use before treatment were identified to examine whether trajectory classes and their interactions with treatment arm (acamprosate or placebo), pretreatment drinking goal (abstinence or a reduction), and time predicted alcohol use outcomes. Results: Three distinct trajectory classes were identified: frequent drinkers, nearly daily drinkers, and consistent daily drinkers. Consistent daily drinkers with a goal of abstinence significantly improved over time on the primary outcome measure of percent days abstinent when compared with frequent and nearly daily drinkers. In addition, all participants with a goal of abstinence, regardless of trajectory class, significantly reduced their percentage of heavy drinking days over time. Conclusions: Patients with an alcohol use disorder who have a drinking goal of abstinence, in particular consistent daily drinkers, may maximally benefit from alcohol use disorder treatment, including the use of medication, in a primary care setting.


PubMed | CB and 7175 and Bowles Center for Alcohol Studies
Type: Journal Article | Journal: Psychopharmacology | Year: 2016

Anxiety during pregnancy has been linked to adverse maternal health outcomes, including postpartum depression (PPD). However, there has been limited study of biological mechanisms underlying behavioral predictors of PPD during pregnancy.Considering the shared etiology of chronic stress amongst antenatal behavioral predictors, the primary goal of this pilot study was to examine associations among stress-related physiological factors (including GABA-ergic neurosteroids) and stress-related behavioral indices of anxiety during pregnancy.Fourteen nulliparous women in their second trimester of a singleton pregnancy underwent speech and mental arithmetic stress, following a 2-week subjective and objective recording of sleep-wake behavior.Lower cortisol, progesterone, and a combined measure of ALLO+pregnanolone throughout the entire stressor protocol (area under the curve, AUC) were associated with greater negative emotional responses to stress, and lower cortisol AUC was associated with worse sleep quality. Lower adrenocorticotropic hormone was associated with greater anxious and depressive symptoms. Stress produced paradoxical reductions in cortisol, progesterone, and a combined measure of allopregnanolone+pregnanolone, while tetrahydrodeoxycorticosterone levels were elevated.These data suggest that cortisol, progesterone, and ALLO+pregnanolone levels in the second trimester of pregnancy are inversely related to negative emotional symptoms, and the negative impact of acute stress challenge appears to exert its effects by reducing these steroids to further promote negative emotional responses.


Qin L.,Bowles Center for Alcohol Studies | Crews F.T.,Bowles Center for Alcohol Studies
Journal of Neuroinflammation | Year: 2012

Background: Activation of microglia causes the production of proinflammatory factors and upregulation of NADPH oxidase (NOX) that form reactive oxygen species (ROS) that lead to neurodegeneration. Previously, we reported that 10 daily doses of ethanol treatment induced innate immune genes in brain. In the present study, we investigate the effects of chronic ethanol on activation of NOX and release of ROS, and their contribution to ethanol neurotoxicity.Methods: Male C57BL/6 and NF-κB enhanced GFP mice were treated intragastrically with water or ethanol (5 g/kg, i.g., 25% ethanol w/v) daily for 10 days. The effects of chronic ethanol on cell death markers (activated caspase-3 and Fluoro-Jade B), microglial morphology, NOX, ROS and NF-κB were examined using real-time PCR, immunohistochemistry and hydroethidine histochemistry. Also, Fluoro-Jade B staining and NOX gp91 phoximmunohistochemistry were performed in the orbitofrontal cortex (OFC) of human postmortem alcoholic brain and human moderate drinking control brain.Results: Ethanol treatment of C57BL/6 mice showed increased markers of neuronal death: activated caspase-3 and Fluoro-Jade B positive staining with Neu-N (a neuronal marker) labeling in cortex and dentate gyrus. The OFC of human post-mortem alcoholic brain also showed significantly more Fluoro-Jade B positive cells colocalized with Neu-N, a neuronal marker, compared to the OFC of human moderate drinking control brain, suggesting increased neuronal death in the OFC of human alcoholic brain. Iba1 and GFAP immunohistochemistry showed activated morphology of microglia and astrocytes in ethanol-treated mouse brain. Ethanol treatment increased NF-κB transcription and increased NOX gp91 phoxat 24 hr after the last ethanol treatment that remained elevated at 1 week. The OFC of human postmortem alcoholic brain also had significant increases in the number of gp91 phox+ immunoreactive (IR) cells that are colocalized with neuronal, microglial and astrocyte markers. In mouse brain ethanol increased gp91 phoxexpression coincided with increased production of O 2 -and O 2 -- derived oxidants. Diphenyleneiodonium (DPI), a NOX inhibitor, reduced markers of neurodegeneration, ROS and microglial activation.Conclusions: Ethanol activation of microglia and astrocytes, induction of NOX and production of ROS contribute to chronic ethanol-induced neurotoxicity. NOX-ROS and NF-κB signaling pathways play important roles in chronic ethanol-induced neuroinflammation and neurodegeneration. © 2012 Qin and Crews; licensee BioMed Central Ltd.


Fish E.W.,Bowles Center for Alcohol Studies | Holloway H.T.,Bowles Center for Alcohol Studies | Rumple A.,Bowles Center for Alcohol Studies | Baker L.K.,Bowles Center for Alcohol Studies | And 4 more authors.
Behavioural Brain Research | Year: 2016

Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8 g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers. © 2016 Elsevier B.V.


Lovinger D.M.,U.S. National Institutes of Health | Kash T.L.,Bowles Center for Alcohol Studies
Alcohol research : current reviews | Year: 2015

Long-lasting changes in synaptic function (i.e., synaptic plasticity) have long been thought to contribute to information storage in the nervous system. Although synaptic plasticity mainly has adaptive functions that allow the organism to function in complex environments, it is now clear that certain events or exposure to various substances can produce plasticity that has negative consequences for organisms. Exposure to drugs of abuse, in particular ethanol, is a life experience that can activate or alter synaptic plasticity, often resulting in increased drug seeking and taking and in many cases addiction.Two brain regions subject to alcohol's effects on synaptic plasticity are the striatum and bed nucleus of the stria terminalis (BNST), both of which have key roles in alcohol's actions and control of intake. The specific effects depend on both the brain region analyzed (e.g., specific subregions of the striatum and BNST) and the duration of ethanol exposure (i.e., acute vs. chronic). Plastic changes in synaptic transmission in these two brain regions following prolonged ethanol exposure are thought to contribute to excessive alcohol drinking and relapse to drinking. Understanding the mechanisms underlying this plasticity may lead to new therapies for treatment of these and other aspects of alcohol use disorder.


Huang M.M.,Bowles Center for Alcohol Studies | Overstreet D.H.,Bowles Center for Alcohol Studies | Overstreet D.H.,University of North Carolina at Chapel Hill | Knapp D.J.,Bowles Center for Alcohol Studies | And 9 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2010

In abstinent alcoholics, stress induces negative affect - a response linked to craving and relapse. In rats, repeated stresses at weekly intervals before 5-day ethanol diet sensitize withdrawalinduced anxiety-like behavior ("anxiety") that is blocked by a corticotrophin-releasing factor 1 (CRF-1)-receptor antagonist. Current experiments were performed to identify brain sites that support CRF involvement in stress sensitization of ethanol withdrawal-induced anxiety-like behavior. First, different doses of CRF microinjected weekly into the central amygdala (CeA) before ethanol exposure produced a dose-related sensitization of anxiety during ethanol withdrawal. Subsequently, CRF microinjection into the basolateral amygdala, dorsal raphe nucleus (DRN), or dorsal bed nucleus of the stria terminalis (d-BNST) also sensitized ethanol withdrawal-induced anxiety. In contrast, sensitization of ethanol withdrawal-induced anxiety was not observed after weekly CRF administration into the ventral-BNST, CA1-hippocampal region, or hypothalamic-paraventricular nucleus. Then, experiments documented the CRF receptor subtype responsible for CRF and stress sensitization of withdrawal-induced anxiety. Systemic administration of a CRF-1 receptor antagonist before CRF microinjection into the CeA, DRN, or d-BNST prevented CRF-induced sensitization of anxiety during ethanol withdrawal. Furthermore, repeated microinjections of urocortin-3, a CRF-2 receptor agonist, into the CRF-positive sites did not sensitize anxiety after withdrawal from ethanol. Finally, microinjection of a CRF-1 receptor antagonist into the CeA, DRN, or d-BNST before stress blocked sensitization of anxiety-like behavior induced by the repeated stress/ethanol withdrawal protocol. These results indicate that CRF released by stress acts on CRF-1 receptors within specific brain regions to produce a cumulative adaptation that sensitizes anxiety-like behavior during withdrawal from chronic ethanol exposure. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.

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