Alcohol RSS feed: Current Issue. Alcohol is an international, peer-reviewed journal that is devoted to publishing multi-disciplinary biomedical research on all aspects of the actions or effects of alcohol on the nervous system or on other organ systems. Emphasis is given to studies into the causes and consequences of alcohol abuse and alcoholism, and biomedical aspects of diagnosis, etiology, treatment or prevention of alcohol-related health effects. Intended for both research scientists and practicing clinicians, the journal publishes original research on the neurobiological, neurobehavioral, and pathophysiological processes associated with alcohol drinking, alcohol abuse, alcohol-seeking behavior, tolerance, dependence, withdrawal, protracted abstinence, and relapse. In addition, the journal reports studies on the effects alcohol on brain mechanisms of neuroplasticity over the life span, biological factors associated with adolescent alcohol abuse, pharmacotherapeutic strategies in the treatment of alcoholism, biological and biochemical markers of alcohol abuse and alcoholism, pathological effects of uncontrolled drinking, biomedical and molecular factors in the effects on liver, immune system, and other organ systems, and biomedical aspects of fetal alcohol spectrum disorder including mechanisms of damage, diagnosis and early detection, treatment, and prevention. Articles are published from all levels of biomedical inquiry, including the following: molecular and cellular studies of alcohol's actions in vitro and in vivo ; animal model studies of genetic, pharmacological, behavioral, developmental or pathophysiological aspects of alcohol; human studies of genetic, behavioral, cognitive, neuroimaging, or pathological aspects of alcohol drinking; clinical studies of diagnosis (including dual diagnosis), treatment, prevention, and epidemiology. The journal will publish 9 issues per year; the accepted abbreviation for Alcohol for bibliographic citation is Alcohol . Alcohol subscribes to the tenets of The Farmington Consensus (see http://www.elsevier.com/framework_products/promis_misc/525453fc.pdf or http://www1.elsevier.com/homepage/sab/alcohol/fconsensus.htm ). Submission of a paper to the journal will be taken as evidence that the authors have complied with the tenets set forth in the Consensus. All submitted material will be subject to peer review. Alcohol considers three types of manuscripts for publication: - Original research articles are full-length reports of the authors' original research addressing topics consistent with the Aims and Scope of the journal. Submissions outside the scope of the journal, or incomplete or fragmentary submissions, will not be considered. - Rapid communications are original, high-quality manuscripts that describe new data of high impact and major importance to the field. These contributions are typically short (e.g., 4 journal pages), and will be peer-reviewed by at least one expert in the field of the research and an Editor, and will be either accepted with minimal or no revisions or rejected. Publication of accepted rapid communications will be expedited. - Invited review articles will be considered for publication, upon invitation from the Editor-in-Chief, as full-length papers or mini-reviews. These contributions will be peer-reviewed. Contact the Editor-in-Chief concerning the suitability of a topic for an invited review. There are no page charges for articles published in Alcohol , and the current practice is to provide the corresponding author with 50 free reprints of his/her article. Effective May 2006, authors from all countries are invited to submit manuscripts, complete in all respects and following the Instructions to Authors (revised May 2006), to Charles R. Goodlett, Editor-in-Chief, via Elsevier electronic submission at http://ees.elsevier.com/alcohol Contact for questions: Charles R. Goodlett Editor-in-Chief, Alcohol Department of Psychology IUPUI 402 North Blackford Street Indianapolis, IN 46202-3275 Tel: +1-317 274-6772 Fax: +1-317 278-7181 E-mail: alcojrnl@iupui.edu http://www.alcoholjournal.org/?rss=yesElsevier Inc.en Published by Elsevier Inc. Alcohol0741-8329464June 2012 Published by Elsevier Inc. healthpermissions@elsevier.comhttp://www.alcoholjournal.org/article/PIIS0741832911005246/abstract?rss=yesExcessive alcohol use, alcohol abuse, and relapse to heavy drinking are all characteristic of alcohol use disorders. Brain circuits controlling reward, appetitive behavior, decision making and habit formation have been implicated in these aspects of alcohol seeking and intake in a variety of animals. A number of studies over the past 10–15 years have also generated evidence that brain circuits implicated in stress responsiveness also regulate alcohol drinking behavior (reviewed in ). The extended amygdala, a series of interconnected limbic brain nuclei that includes (among other regions) the nucleus accumbens, central amygdala and bed nucleus of the stria terminalis (BNST) has emerged as a circuit key to the interface of stress- and alcohol-related behaviors. Interactions of these brain regions with “limbic” cortical areas provide influences from brain circuitry involved in context recognition, affective control and decision making. Thus, the extended amygdala is poised to integrate an array of environmental information that can influence alcohol-related behaviors. In addition, evidence of direct alcohol effects on this circuitry has emerged from studies using animal models. Overall, this circuit is most strongly linked to alcohol intake driven by the need to relieve negative outcomes of abstinence/withdrawal following a history of alcohol consumption. Withdrawal itself is stressful, and can also be impacted by stressful environmental events. Studies in several laboratories are now focusing on how stress, past drinking history and the extended amygdala circuitry contribute to relapse to drinking in rodent models.Young investigators stress alcohol-induced neuroadaptations in extended amygdalaDavid M. Lovinger10.1016/j.alcohol.2011.11.001Alcohol 46, 4 (2012)2012-03-22Alcohol2012-03-22464S0741-8329(11)X0012-5299300http://www.alcoholjournal.org/article/PIIS0741832912000614/abstract?rss=yesThe growing health burdens of alcohol addiction and stress-related disorders demand novel treatment strategies and new advances in biomedical research. Alcoholism and Stress: A Framework for Future Treatment Strategies is an international meeting dedicated to developing preventive strategies and pharmacotherapeutic remedies for stress- and alcohol-related disorders. This was the second conference on this topic hosted by Drs. Roberto and Koob in May 2011, and like the inaugural conference, the meeting was held in Volterra, Italy. This conference is the only international meeting of its kind. Its primary purpose is to establish an international effort between both basic researchers and clinicians to develop prevention strategies and pharmacotherapeutic remedies for alcohol disorders. The meeting provided a platform for the world's preeminent scientists in alcoholism and stress research to present their latest findings through plenary lectures, symposia, posters, and roundtable discussions. Presentations represented research in molecular and cellular biology, epidemiology, behavioral, and clinical alcohol research.Introduction to Young Investigator Award Symposium: Symposium XII: Young Investigator AwardMarisa Roberto, Thomas L. Kash, Patrick J. Mulholland, Vincent N. Marty, Nicholas W. Gilpin, Brendan M. Walker10.1016/j.alcohol.2012.04.001Alcohol 46, 4 (2012)2012-04-30Alcohol2012-04-30464S0741-8329(11)X0012-5301302http://www.alcoholjournal.org/article/PIIS0741832912000365/abstract?rss=yesAbstract: There is a growing body of evidence that suggests that stress and anxiety can influence the development of alcohol use disorders. This influence is believed to be due in part to persistent adaptations in discrete brain regions that underlie stress responsivity. One structure that has been proposed to be a site of important neuroadaptations underlying this behavior is the extended amygdala. The extended amygdala is a series of extensively inter-connected limbic structures including the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST). These structures are critical regulators of behavioral and physiological activation associated with anxiety. Additionally, numerous reports have suggested that these regions are involved in increased drinking behavior associated with chronic alcohol exposure and withdrawal. The focus of this review will be to discuss the role of the BNST in regulation of behavior, to provide some insight in to the circuitry of the BNST, and to discuss the actions of the biogenic amines, serotonin, dopamine and norepinephrine, in the BNST.The role of biogenic amine signaling in the bed nucleus of the stria terminals in alcohol abuseThomas Louis Kash10.1016/j.alcohol.2011.12.004Alcohol 46, 4 (2012)2012-03-27Alcohol2012-03-27464S0741-8329(11)X0012-5303308http://www.alcoholjournal.org/article/PIIS0741832911005258/abstract?rss=yesAbstract: Small-conductance, calcium-activated potassium (KCa2) channels influence neuronal firing properties, intrinsic excitability, and NMDA receptor-dependent synaptic responses and plasticity. In this mini-review, we discuss new evidence that chronic alcohol-associated plasticity critically involves KCa2 channels in hippocampus, ventral tegmental area, and nucleus accumbens. KCa2 channel activity can modulate the magnitude of excitation of midbrain dopamine neurons induced by acute alcohol exposure. Emerging evidence indicates that KCa2 channels regulate neuroadaptations to chronic alcohol that contribute to withdrawal hyperexcitability and escalation of voluntary alcohol consumption. Restoring KCa2 channel activity can attenuate the severity of the alcohol withdrawal syndrome in vivo and withdrawal-associated neurotoxicity in vitro. Pharmacological modulation of KCa2 channels can bi-directionally influence drinking behavior in rat and mouse models of voluntary alcohol consumption. Collectively, these studies using various rodent models have clearly indicated a central role for KCa2 channels in the neuroplasticity of chronic alcohol exposure. In addition, accumulating evidence suggests that KCa2 channels are a novel therapeutic target to alleviate the symptoms of alcohol withdrawal and reduce high amounts of alcohol drinking.KCa2 channels: Novel therapeutic targets for treating alcohol withdrawal and escalation of alcohol consumptionPatrick J. Mulholland10.1016/j.alcohol.2011.11.002Alcohol 46, 4 (2012)2012-04-05Alcohol2012-04-05464S0741-8329(11)X0012-5309315http://www.alcoholjournal.org/article/PIIS0741832911005234/abstract?rss=yesAbstract: Chronic and excessive alcohol drinking lead to alcohol dependence and loss of control over alcohol consumption, with serious detrimental health consequences. Chronic alcohol exposure followed by protracted withdrawal causes profound alterations in the brain reward system that leads to marked changes in reinforcement mechanisms and motivational state. These long-lasting neuroadaptations are thought to contribute to the development of cravings and relapse. The nucleus accumbens (NAcc), a central component of the brain reward system, plays a critical role in alcohol-induced neuroadaptive changes underlying alcohol-seeking behaviors. Here we review the findings that chronic alcohol exposure produces long-lasting neuroadaptive changes in various ion channels that govern intrinsic membrane properties and neuronal excitability, as well as excitatory and inhibitory synaptic transmission in the NAcc that underlie alcohol-seeking behavior during protracted withdrawal.Effects of alcohol on the membrane excitability and synaptic transmission of medium spiny neurons in the nucleus accumbensVincent N. Marty, Igor Spigelman10.1016/j.alcohol.2011.12.002Alcohol 46, 4 (2012)2012-03-26Alcohol2012-03-26464S0741-8329(11)X0012-5317327http://www.alcoholjournal.org/article/PIIS0741832912000651/abstract?rss=yesAbstract: The central amygdala (CeA) is uniquely situated to function as an interface between stress- and addiction-related processes. This brain region has long been attributed an important role in aversive (e.g., fear) conditioning, as well as the negative emotional states that define alcohol dependence and withdrawal. The CeA is the major output region of the amygdala and receives complex inputs from other amygdaloid nuclei as well as regions that integrate sensory information from the external environment (e.g., thalamus, cortex). The CeA is functionally and anatomically divided into lateral and medial subdivisions that themselves are interconnected and populated by inhibitory interneurons and projections neurons. Neuropeptides are highly expressed in the CeA, particularly in the lateral subdivision, and the role of many of these peptides in regulating anxiety- and alcohol-related behaviors has been localized to the CeA. This review focuses on two of these peptides, corticotropin-releasing factor (CRF) and neuropeptide Y (NPY), that exhibit a high degree of neuroanatomical overlap (e.g., in CeA) and largely opposite behavioral profiles (e.g., in regulating anxiety- and alcohol-related behavior). CRF and NPY systems in the CeA appear to be recruited and/or up-regulated during the transition to alcohol dependence. These and other neuropeptides may converge on GABA synapses in CeA to control projection neurons and downstream effector regions, thereby translating negative affective states into anxiety-like behavior and excessive alcohol consumption.Corticotropin-releasing factor (CRF) and neuropeptide Y (NPY): Effects on inhibitory transmission in central amygdala, and anxiety- & alcohol-related behaviorsNicholas W. Gilpin10.1016/j.alcohol.2011.11.009Alcohol 46, 4 (2012)2012-05-07Alcohol2012-05-07464S0741-8329(11)X0012-5329337http://www.alcoholjournal.org/article/PIIS0741832912000353/abstract?rss=yesAbstract: This article represents one of five contributions focusing on the topic “Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure” that were developed by awardees participating in the Young Investigator Award Symposium at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms.Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent processBrendan M. Walker10.1016/j.alcohol.2012.01.001Alcohol 46, 4 (2012)2012-03-30Alcohol2012-03-30464S0741-8329(11)X0012-5339348http://www.alcoholjournal.org/article/PIIS0741832912000389/abstract?rss=yesAbstract: It is widely accepted that stress, anxiety, depression and alcohol abuse-related disorders are in large part controlled by corticotropin-releasing factor (CRF) receptors. However, evidence is accumulating that some of the actions on these receptors are mediated not by CRF, but by a family of related Urocortin (Ucn) peptides Ucn1, Ucn2 and Ucn3. The initial narrow focus on CRF as the potential main player acting on CRF receptors appears outdated. Instead it is suggested that CRF and the individual Ucns act in a complementary and brain region-specific fashion to regulate anxiety-related behaviors and alcohol consumption. This review, based on a symposium held in 2011 at the research meeting on “Alcoholism and Stress” in Volterra, Italy, highlights recent evidence for regulation of these behaviors by Ucns. In studies on stress and anxiety, the roles of Ucns, and in particular Ucn1, appear more visible in experiments analyzing adaptation to stressors rather than testing basal anxiety states. Based on these studies, we propose that the contribution of Ucn1 to regulating mood follows a U-like pattern with both high and low activity of Ucn1 contributing to high anxiety states. In studies on alcohol use disorders, the CRF system appears to regulate not only dependence-induced drinking, but also binge drinking and even basal consumption of alcohol. While dependence-induced and binge drinking rely on the actions of CRF on CRFR1 receptors, alcohol consumption in models of these behaviors is inhibited by actions of Ucns on CRFR2. In contrast, alcohol preference is positively influenced by actions of Ucn1, which is capable of acting on both CRFR1 and CRFR2. Because of complex distribution of Ucns in the nervous system, advances in this field will critically depend on development of new tools allowing site-specific analyses of the roles of Ucns and CRF.Urocortins: CRF's siblings and their potential role in anxiety, depression and alcohol drinking behaviorAndrey E. Ryabinin, Michael M. Tsoory, Tamas Kozicz, Todd E. Thiele, Adi Neufeld-Cohen, Alon Chen, Emily G. Lowery-Gionta, William J. Giardino, Simranjit Kaur10.1016/j.alcohol.2011.10.007Alcohol 46, 4 (2012)2012-03-23Alcohol2012-03-23464S0741-8329(11)X0012-5349357http://www.alcoholjournal.org/article/PIIS0741832912000274/abstract?rss=yesAbstract: This review represents the focus of a symposium that was presented at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 and organized/chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN/KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders.Targeting dynorphin/kappa opioid receptor systems to treat alcohol abuse and dependenceBrendan M. Walker, Glenn R. Valdez, Jay P. McLaughlin, Georgy Bakalkin10.1016/j.alcohol.2011.10.006Alcohol 46, 4 (2012)2012-03-29Alcohol2012-03-29464S0741-8329(11)X0012-5359370http://www.alcoholjournal.org/article/PIIS0741832912000286/abstract?rss=yesAbstract: Early childhood stress is a risk factor for the development of substance-abuse disorders. A nonhuman primate model of early life stress, social impoverishment through nursery-rearing rather than mother-rearing, has been shown to produce increased impulsive and anxiety-like behaviors, cognitive and motor deficits, and increased alcohol consumption. These behavioral changes have been linked to changes in cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin (5-HT) metabolite. The effects of different rearing conditions on ethanol drinking and three measures of 5-HT function in the central nervous system were evaluated, including CSF 5-HIAA levels and tissue levels of 5-HT and 5-HIAA in brain samples. Brain samples were taken from the dorsal caudate, putamen, substantia nigra (SN) pars reticulata, SN pars compacta and hippocampus. There was a clear effect of rearing condition on the 5-HT system. Overall 5-HIAA and 5-HIAA/5-HT ratio measures of 5-HT turnover were significantly lower in nursery reared compared to mother-reared animals. In addition, there was a strong within-subject correlation between CSF and brain tissue 5-HIAA levels. Ethanol drinking was greater in nursery reared monkeys, consistent with previous results. These findings show that CSF 5-HIAA measurements can be used to predict brain 5-HT activity that may be involved in behavioral outcomes such as anxiety and alcohol consumption. Thus, CSF sampling may provide a minimally invasive test for neurochemical risk factors related to alcohol abuse.Effects of early life stress on drinking and serotonin system activity in rhesus macaques: 5-hydroxyindoleacetic acid in cerebrospinal fluid predicts brain tissue levelsKimberly N. Huggins, Tiffany A. Mathews, Jason L. Locke, Kendall T. Szeliga, David P. Friedman, Allyson J. Bennett, Sara R. Jones10.1016/j.alcohol.2011.11.003Alcohol 46, 4 (2012)2012-03-26Alcohol2012-03-26464S0741-8329(11)X0012-5371376http://www.alcoholjournal.org/article/PIIS0741832912000249/abstract?rss=yesAbstract: Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol.Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): Implications for alcohol-induced behavioral plasticityAlexis W. Ary, Debra K. Cozzoli, Deborah A. Finn, John C. Crabbe, Marlin H. Dehoff, Paul F. Worley, Karen K. Szumlinski10.1016/j.alcohol.2011.10.003Alcohol 46, 4 (2012)2012-03-23Alcohol2012-03-23464S0741-8329(11)X0012-5377387http://www.alcoholjournal.org/article/PIIS0741832912000298/abstract?rss=yesAbstract: NMDA receptors become a major contributor to acute ethanol intoxication effects at high concentrations as ethanol binds to a unique site on the receptor and inhibits glutamatergic activity in multiple brain areas. Although a convincing body of literature exists on the ability of NMDA receptor antagonists to mimic and worsen cellular and behavioral ethanol effects, receptor agonists have been less well-studied. In addition to a primary agonist site for glutamate, the NMDA receptor contains a separate co-agonist site that responds to endogenous amino acids glycine and d-serine. d-serine is both selective for this co-agonist site and potent in boosting NMDA dependent activity even after systemic administration. In this study, we hypothesized that exogenous d-serine might ameliorate some acute ethanol behaviors by opposing NMDA receptor inhibition. We injected adult male C57 mice with a high concentration of d-serine at various time windows relative to ethanol administration and monitored sedation, motor coordination and voluntary ethanol drinking. d-serine (2.7 g/kg, ip) prolonged latency to a loss of righting reflex (LoRR) and shortened LoRR duration when given 15 min before ethanol (3 g/kg) but not when it was injected with or shortly after ethanol. Blood samples taken at sedative recovery and at fixed time intervals revealed no effect of d-serine on ethanol concentration but an ethanol-induced decrease in l-serine and glycine content was prevented by acute d-serine pre-administration. d-serine had no effect on ethanol-induced (2 g/kg) rotarod deficits in young adult animals but independently and interactively degraded motor performance in a subset of older mice. Finally, a week-long series of daily ip injections resulted in a 50% decrease in free choice ethanol preference for d-serine treated animals compared to saline-injected controls in a two-bottle choice experiment.Timing-dependent reduction in ethanol sedation and drinking preference by NMDA receptor co-agonist d-serineAmber Lockridge, Gabriel Romero, Justin Harrington, Brett Newland, Zi Gong, Andrew Cameron, Li-Lian Yuan10.1016/j.alcohol.2011.11.004Alcohol 46, 4 (2012)2012-03-26Alcohol2012-03-26464S0741-8329(11)X0012-5389400