Cycle Of Withdrawal Research Articles

“You get good at becoming secretive, at hiding it.” Shame and loneliness: the mental health impacts of skin picking disorder

PurposeThe purpose of this paper is to report on a study into the lived experience of skin picking disorder (SPD) and to explore the psychological impact of the disorder.Design/methodology/approachResearchers employed a qualitative phenomenological approach, using Interpretative phenomenological analysis (IPA).FindingsThe study found that the sense of shame, common among participants, led to self-stigma, hiding, concealing and avoidance. Shame of SPD also interplayed with and compounded the shame of loneliness.Research limitations/implicationsLimitations included a lack of a longitudinal component to the work. This is deemed important, as both the SPD and the experience of loneliness can shift over time as circumstances change, and individuals develop strategies for coping or, conversely, experience a worsening of the condition and the shame, loneliness and social isolation it can induce.Practical implicationsThis study draws attention to the complex nature of both SPD and loneliness. It highlights how those living with the disorder are reluctant to seek help, resulting in low rates of treatment access and distrust in health providers.Social implicationsAs SPD is little understood, it can be erroneously deemed a “choice”; seldom discussed as a condition, it can lead to exclusion and withdrawal. The sense of shame of both appearance and behaviour interplays with and compounds the shame of loneliness and can force the individual into a further cycle of withdrawal and isolation.Originality/valueWhile research suggests SPD should be acknowledged as a public health issue, research and literature is still relatively limited, and there are no qualitative phenomenological studies as yet that report on the lived experience of SPD.

Large-scale storage of hydrogen in salt caverns for carbon footprint reduction

This article presents a geomechanical appraisal of green hydrogen (H2) storage in salt caverns opened by solution mining as a technical contribution to carbon footprint reduction. The location of the salt cavern is speculative, within possible limits to be found in the salt deposits in the Gulf of Mexico of the USA, as the aim is to demonstrate the technical feasibility of the concept. It presents the conceptual design of the wells used for the solution mining of the caverns and the operation cycle of injection and withdrawal of hydrogen. The contribution of the study presented stems from the methodology adopted in the simulation of the geomechanical structural behavior of the salt cavern and in its design for storing hydrogen, which has thermomechanical properties more complex than natural gas. The numerical simulation considers the nonlinear physical viscoelastic and elastoplastic phenomena, with different constitutive laws for representing the geomechanical behavior of geomaterials. The constitutive laws based on deformation mechanisms are used (multi-mechanisms of deformation – M.D.) to simulate the creep of the salt rock. The article also presents a protocol for sizing the caverns, considering more than 40 years of experience in the design of conventional and solution mining of rock salt. It presents the concept of admissible halite creep strain and safety factors necessary to establish a stress belt that avoids hydrogen leaks at all stages of cavern construction and hydrogen storage. Using this methodology, the authors found that the cavern studied (220 m in height and 95 m in diameter) can hold 11,968,000 kg of working hydrogen.

Method of increasing the efficiency of the switch node of the information communication network for special purpose in the conditions of combat use

The peculiarity of the special purpose communication information network is that its functioning is influenced by the tactical situation. In particular, it determines the intensity of the flow of packets with information about the enemy's moving objects from reconnaissance and signaling complexes to the switching node, and from it to the control point and means of destruction, depending on the probable nature of enemy action. In combat applications, the information network operates simultaneously with fast and slow packet flows.
 At the same time, the packet delay in the switching node should not exceed the allowable value. Excessive packet delay results in the loss of relevance of transmitted messages and, consequently, in the loss of intelligence data. The proposed method of eliminating excessive delay involves the formation of two queues of packets in the switching node. Withdrawal of service packages from two queues is carried out using a new adaptive procedure.
 An adaptive switch has been introduced into the structure of the switching node, designed to withdraw packets from queues to the packet service system. When selecting a packet queue, the adaptive switch compares the number of service requests from each queue. The method assumes that the number of service requests from the fast packet flow queue determines the number of packets that are in the queue. The number of requests that are formed from the queue of slow-flow packets has two components: the number of real and the number of conditional requests. Actual applications take into account the number of packets in the queue.
 Real requests take into account the number of packets in the queue. Conditional requests take into account the delay time, since for each missed cycle of the packet's withdrawal from the slow flow queue, the adaptive switch generates a conditional request. Therefore, the number of requests for a slow stream grows even without packets entering the queue. A comparative study of options for implementing the adaptive procedure has been carried out. The proposed method for eliminating excessive packet delay in the switching node provides an increase in the efficiency of the functioning of a special-purpose information network as a whole.

Physical mechanisms associated with the intense lightning over Indian region

AbstractIndian subcontinent receives ~80% of its annual total rainfall during Indian summer monsoon (ISM) and since last 100 years the prediction of interannual variability of ISM is limited due to incomplete understanding of various processes and their localized influence on the development of varying scales of convective systems. The present study reports that the intense lightning contributed from the deepest convections occurring over Indian subcontinent are concentrated in four specific regions: (a) southwest coast, (b) Gangetic‐Brahmaputra plain, (c) Himalayan foothills and (d) southeast coast. The spatial and temporal variations of deep convections, size of “convection fractions” and associated physical mechanisms are described. It shows an annual cycle of systematic onset and withdrawal of deep convections and associated lightning depending on region and season. The southwest coast region is developing very deep convections during premonsoon and postmonsoon seasons but less lightning during monsoon. While Arabian Sea sources high moisture to this region in monsoon season, the orographic lift of low‐level westerlies by Western Ghats may effectively assist the warm rain processes and produce highest rainfall, low lightning and low area of deep convections. Highest flash rates, high number of days with lightning and higher area of convection are observed in Gangetic‐Brahmaputra plain but relatively lower rainfall compared to southwest coast region during monsoon. The sustained strong updrafts over the Gangetic‐Brahmaputra plain region are supported by the moisture source from warmer Bay of Bengal, incidence of monsoon trough and the continental heating. Significant lightning activity observed in northwest part of Himalayan foothills during winter is associated with Western Disturbances (WD) phenomena. The diurnal variation of lightning flash rate and size of “convective fraction” in these regions show two modes at 1200 and 1800 UTC and it indicates active day time surface heating and nocturnal cooling processes together contribute to total rainfall.

Arrested Development: Organizational and Entrepreneurial Sensemaking in a Maker Space

Entrepreneurial sensemaking – the process by which entrepreneurs determine and refine both the nature of their offering and the model through which they will distribute that offering – is difficult. To facilitate the process, entrepreneurial support organizations (ESOs), like incubators and accelerators, have emerged all over the world. Yet, entrepreneurial success stories emanating from ESOs have been conspicuously few. In a two-year-long inductive, grounded theory study of a maker space – the latest iteration of ESO, focused on shared access to tools, collaboration, and the development of technical capabilities, we identify three orientations entrepreneurs use to relate to maker spaces. Two of these are reinforced by the maker space, while the third is not. Concerning the latter, the unexpected mismatch between individuals enacting this orientation and those reinforced by the maker space encumbers entrepreneurial sensemaking, eliciting doubt within them as to whether they can succeed as entrepreneurs and/or whether their ventures can succeed in the market. This leads to a cycle of self-defeat and withdrawal. However, the two orientations that are reinforced by the maker space are no guarantee of success either. In these cases, ventures become dependent on the maker space through the cost advantages its resources provide, creating a cycle of entrenchment that makes it difficult – if not impossible – for the business to ever leave the maker space. Ultimately, our study contributes to theory development on both entrepreneurial action and sensemaking, while informing the phenomenon-based literature on maker spaces and offering a process- based explanation for the few entrepreneurial success stories coming out of ESOs.

Self-regulation and social behavior during sleep deprivation.

An emerging literature is specifically focusing on the effects of sleep deprivation on aspects of social functioning and underlying neural changes. Two critical facets of social behavior emerge that are negatively impacted by sleep deprivation-self-regulation, which includes behavioral and emotional regulation, and social monitoring, which includes perceiving and interpreting cues relating to self and others. Sleep deprived individuals performing tasks with social components show altered brain activity in areas of the prefrontal cortex implicated in self-control, inhibition, evaluation, and decision-making, in proximity to mesocorticolimbic pathways to reward and emotional processing areas. These cognitive changes lead to increased reward seeking and behaviors that promote negative health outcomes (such as increased consumption of indulgence foods). These changes also lead to emotional disinhibition and increased responses to negative stimuli, leading to reductions in trust, empathy, and humor. Concomitant attentional instability leads to impaired social information processing, impairing individual and team performance and increasing likelihood of error, incident, and injury. Together, changes to reward seeking, the foundational components of social interaction, and interpretation of social cues, can result in unpleasant or deviant behavior. These behaviors are perceived and negatively responded to by others, leading to a cycle of conflict and withdrawal. Further studies are necessary and timely. Educational and behavioral interventions are required to reduce health-damaging behaviors, and to reduce emotionally-laden negative interpretation of sleep-deprived exchanges. This may assist with health, and with team cohesion (and improved performance and safety) in the workplace and the home.

Sleep loss causes social withdrawal and loneliness

Loneliness and social isolation markedly increase mortality risk, and are linked to numerous mental and physical comorbidities, including sleep disruption. But does sleep loss causally trigger loneliness? Here, we demonstrate that a lack of sleep leads to a neural and behavioral phenotype of social withdrawal and loneliness; one that can be perceived by other members of society, and reciprocally, makes those societal members lonelier in return. We propose a model in which sleep loss instigates a propagating, self-reinforcing cycle of social separation and withdrawal.

The Effect of Compulsory and Voluntary Exercise on Morphine-Induced Conditioned Place Preference in Rats

Background: Addiction is described as a condition in which individuals are not able to control their drug use despite long-term negative consequences. Non-drug addiction or behavioral addiction such as exercise can mimic similar physiological changes in the brain and reward circuit enhancement. Psychological dependence of drug abuse, which is characterized by drug seeking behaviors will develop an ongoing cycle of drug withdrawal and relapse. Moreover, exercise has two bimodal effects; it may decrease drug seeking in a physiologic range and it may increase drug seeking when it is taken in large quantity. The current study aimed to investigate and compare the effects of voluntary and compulsory exercise on male rats’ tendency towards using morphine. Methods: We included 32 male rats that were 2 months of age. After 2-weeks of compulsory and voluntary exercise, all rats were exposed to 5-day conditioned place preference (CPP) in order to evaluate drug-seeking behavior. The CPP scale was obtained by comparing the data from “pre-conditioning” and “post-conditioning” phases and it was used to evaluate morphine-dependence. Results: The results of the current study showed that the rats that received compulsory exercise had significantly less tendency towards morphine (P < 0.05) and voluntary exercise has no significant effect. Conclusions: We conclude that compulsory exercise may reduce psychological dependence on morphine and could also be regarded as a proper complementary method for addiction prevention and preventing relapse.

Substance Abuse and Trauma.

There is a strong, bidirectional link between substance abuse and traumatic experiences. Teens with cooccurring substance use disorders (SUDs) and posttraumatic stress disorder (PTSD) have significant functional and psychosocial impairment. Common neurobiological foundations point to the reinforcing cycle of trauma symptoms, substance withdrawal, and substance use. Treatment of teens with these issues should include a systemic and integrated approach to both the SUD and the PTSD.

Chronic cocaine exposure during pregnancy increases postpartum neuroendocrine stress responses.

The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, Sprague-Dawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 1-20). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured before and after testing throughout the test day, whereas plasma and brain oxytocin concentrations were measured post-testing only. The results obtained indicated increased CORT response after the OFT in CC-treated dams (P ≤ 0.05). CC-treated dams also exhibited altered FST behaviour (P ≤ 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (P ≤ 0.05). Peripheral oxytocin and CORT increased after the FST, regardless of treatment condition (P ≤ 0.05). Changes in stress-responsiveness, both behaviourally and hormonally, may underlie some deficits in maternal behaviour; thus, a clearer understanding of the effect of CC on the stress response system may potentially lead to treatment interventions that could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations.

Changing practice: implementing validated paediatric pain assessment tools

This study attempted to address a lack of evidence-based pain management by implementing validated pain assessment tools across a children's hospital. The method used was action research. The first part of this study where nurses' views of pain tools was elicited has already been reported (Simons and Macdonald, 2004). An action research cycle of negotiation, assessment, diagnosing, planning, action, evaluation and withdrawal was utilized. Data collection occurred at two points in time. Three age-appropriate tools were implemented hospital-wide supported by education and clinical input. A survey of nurses was carried out six months and 12 months post implementation of the tools. At the same time evaluation of the use of the tool was performed. Six months after education and implementation 23 percent of children on 10 wards had a pain tool in use. This had increased to 40 percent six months later. There were many inconsistencies between the replies the nurses gave in relation to their reported use of the tools and the actual use of the tools.

804. In Vivo Correction of a Metabolic Liver Disease by AAV8-Mediated Homologous Recombination

Top of pageAbstract AAV-8 is currently the most efficient serotype to transduce hepatocytes and establish long-lasting transgene expression. However, most vectors remain episomal, integration events are rare and occur randomly. In our study we aimed to prove that targeted integration and homologous recombination by AAV is a feasible method for gene correction in vivo. We therefore used the Fah5961SB mouse model carrying a single bp splice-site mutation causing loss of an exon in the fumarylacetoacetate hydrolase (Fah) gene. Fah mutant mice are a model of the human disease hereditary tyrosinemia type 1 and develop progressive liver failure when the protective drug NTBC is withdrawn. An AAV-8 vector was constructed containing 4.5 kb of the wild-type genomic sequence 5 and 3 of the splice mutation. Importantly, this vector does not contain a Fah expression cassette, but can restore Fah expression only after homologous recombination with the mutant genome. Neonatal (n=6, day of birth, 2x10^11 copies/mouse, intraperitoneal-ip), newborn (n=6, 4 days old, 1x10^11 copies/mouse, ip) and adult mice (n=8, 1x10^11 copies/mouse, portal vein) of both sexes were injected. Corrected hepatocytes were selected in vivo by NTBC withdrawal. Neonatal mice injected at the day of birth showed stabilization or increase of weight at the end of the first cycle of NTBC withdrawal (25 days). Multiple macroscopicallly visible nodules of healthy hepatic tissue were seen when the liver was harvested and histological analysis confirmed Fah+ nodules and thus gene correction at high frequency. Newborns injected at age 4 days and adult mice also showed flattening of weight loss after 25 days off NTBC. Histological analysis in these older mice also showed Fah-positive nodules providing evidence of correction of the point mutation. Further histological and genomic analysis to ascertain the precise quantity and time course of integration events are pending. Our experiments show for the first time in vivo that gene correction by homologous recombination with AAV-8 is possible at reasonable frequencies. Combined with in vivo selection this resulted in complete clinical restoration of an otherwise lethal metabolic liver disease.

Modulation of Ethanol Withdrawal???Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/??-Aminobutyric Acid Ligands

Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal-associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of gamma-aminobutyric acid-modulating drugs on social interaction behavior-an established model of anxiety-in rats exposed to repeated cycles of ethanol treatment and withdrawal. Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl-6, 7-dymerhoxy-4-ethyl-beta-carboline-3-carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Single-dose administration of drugs that enhance or diminish activity at benzodiazepine-gamma-aminobutyric acid- receptors during earlier withdrawals reduced or potentiated, respectively, anxiety-like behavior during later, drug-free withdrawals. These results support the potential of the novel strategy of using prophylactic therapy administered during early withdrawals to ameliorate symptoms of later withdrawals.

Sensitization to morphine withdrawal in guinea-pigs

The aim of this study was to determine whether sensitization occurred to morphine withdrawal. Guinea-pigs were treated twice daily with increasing doses of morphine (10–100 mg/kg s.c.) for 3 days followed by injection of morphine 100 mg/kg on the fourth day. Sixty min after the last morphine injection, animals were withdrawn from morphine with naltrexone, 15 mg/kg s.c., and locomotor activity and all other behaviours scored over 90 min. Animals were then rested for 3 days. This procedure was repeated twice over the next 2 weeks. Control animals were treated with saline for the first two treatment cycles. Guinea-pigs subjected to three cycles of morphine withdrawal showed a significant increase in the total number of withdrawal behaviour counts over the 90-min observation period following the third cycle of withdrawal compared with the first and second withdrawal cycles. However, locomotor activity, a major sign of morphine withdrawal in guinea-pigs, was not significantly increased. Fos-LI was markedly increased in the repeatedly withdrawn animals in several brain regions, including amygdala, dorsal striatum, thalamus, ventral tegmental area, and ventrolateral periaqueductal gray area. It is concluded that sensitization to morphine withdrawal occurs in guinea-pigs.

Effects of CB1 cannabinoid receptor blockade on ethanol preference after chronic alcohol administration combined with repeated re-exposures and withdrawals.

The cannabinoid CB1 receptor antagonist, SR141716A, differentially affects the ethanol preference of chronically alcoholized rats when administered during cycles of ethanol exposure and withdrawal. In this study, ethanol preference was investigated in chronically alcoholized rats that underwent regular withdrawal periods during which the brain cannabinoid CB(1) receptor antagonist, SR141716A, was administered. The cannabinoid receptor antagonist SR141716A, 3 or 10 mg/kg/day, was administered i.p. to Wistar rats at the conclusion of a 4-week period of chronic alcoholization, as they commenced a cycle of alcohol withdrawal for 10 days followed by a period of 10 days chronic ethanol exposure. In a second set of experiments, an additional cycle of ethanol withdrawal and re-exposure was given. Preference for ethanol versus water started at the end of the first or second chronic ethanol re-exposure for a period of at least 30 days. In rats pretreated with the higher dose of SR141716A, ethanol preference during free choice was significantly increased after two ethanol re-exposures. In contrast, pretreatment with the lower SR141716A dose induced no significant change in ethanol intake during the free choice followed by either one or two ethanol re-exposures. SR141716A, 10 mg/kg/day dose, induced a significant increase in ethanol preference which was dependent on both the number of ethanol withdrawals and chronic ethanol re-exposures, while 3 mg/kg/day had no significant effect on ethanol preference.

Imbalance between neuroexcitatory and neuroinhibitory amino acids causes craving for ethanol

Long-term exposure to ethanol leads to an imbalance in different excitatory and inhibitory amino acids. When ethanol consumption is reduced or completely stopped, these imbalances in different amino acids and neurotransmitters are behaviorally expressed in the form of ethanol withdrawal. Glutamate, a major excitatory amino acid, and GABA, a major inhibitory amino acid, are responsible, at least partly, for ethanol withdrawal symptoms. The hypofunction of GABA A receptors and enhanced function of NMDA receptors are suggested to be responsible for the increase in the behavioral susceptibility during ethanol withdrawal. This imbalance between receptors may be exacerbated by repeated withdrawal. Because multiple and repeated periods of chronic ethanol consumption and withdrawal often occur in alcohol abusers, animal studies on the neurochemical changes in different amino acids following chronic ethanol treatment (CET) that is interrupted by repeated ethanol withdrawal episodes may be of clinical relevance for the development of treatment strategies. Brain glutamate increases during the first cycle of ethanol withdrawal, and this increase is much higher during the third cycle of ethanol withdrawal. The elevated glutamate released in the hippocampus during the first cycle of ethanol withdrawal episode was exacerbated in subsequent withdrawal episodes. Acamprosate, a drug used during human alcohol detoxification, is able to completely block the glutamate increase observed during the first as well as the third withdrawal of ethanol. In ethanol-naïve rats, there was no change in the glutamate microdialysate content after an acute ethanol injection. However, when repeated ethanol injections were cued with a vinegar stimulus that had previously been associated with the same ethanol injection, a significant increase in glutamate microdialysate content was assayed. Furthermore, when the cue was omitted, the ethanol injection induced no changes in glutamate microdialysate content in rats that had been previously ethanol conditioned. By comparison, a saline injection had no effect on extracellular glutamate concentration in rats naïve for ethanol as well as in rats daily administered with repeated ethanol injections that were not paired with the cue. It appears probable that these conditioned responses by extracellular glutamate concentrations may participate in the environmental cue-induced conditioned cravings for ethanol that are thought to be related to the high frequency of relapse in detoxified alcoholics.

Prostate cancer cells generated during intermittent androgen ablation acquire a growth advantage and exhibit changes in epidermal growth factor receptor expression.

Intermittent androgen ablation is a palliative treatment option for advanced prostate cancer which is associated with less side effects, improved quality of life of patients, and reduced costs. Regulation of growth and survival of prostate cancer cells during intermittent androgen withdrawal has not been studied in appropriate models yet. Two cycles of androgen withdrawal and supplementation were performed in human prostate cancer cells LNCaP in vitro. Proliferation of prostate cancer cell sublines established after intermittent androgen withdrawal was assessed in the absence or presence of epidermal growth factor (EGF) by protein determination. Cell cycle was analyzed with a flow cytometer. EGF was measured in the supernatants of LNCaP sublines with a commercial ELISA. EGF receptor mRNA and protein were determined by real-time PCR and Western blot, respectively. Basal proliferation rate of all newly generated LNCaP sublines increased over that of the parental LNCaP cell line. The highest stimulation of proliferation by exogenous EGF was observed in parental LNCaP cells. In each LNCaP derivative established during intermittent androgen withdrawal, the percentage of cells in the S phase of cell cycle was higher than that in parental LNCaP cells. EGF levels did not increase during intermittent androgen ablation. The expression of EGF receptor protein decreased following each cycle of androgen ablation and increased subsequently after androgen supplementation. EGF receptor (EGFR) mRNA was regulated in a similar manner in LNCaP derivatives established during the second cycle of intermittent withdrawal. Changes in the expression of the EGF receptor occur during intermittent androgen ablation but they cannot be solely responsible for increased basal proliferation. Alternatively, other ligands and receptors of the EGF system may become overexpressed during prolonged withdrawal and supplementation of androgenic hormones in prostate cancer therapy.

Effects of acamprosate on excitatory amino acids during multiple ethanol withdrawal periods.

Our previous studies on the effects of acamprosate on enhanced locomotion during repeated withdrawals are now extended to the effects of acamprosate on excitatory amino acids in the hippocampus during repeated ethanol withdrawals. In this study, Wistar rats were made ethanol dependent by 4 weeks of vapor inhalation. After this first cycle of chronic ethanol treatment, rats underwent repeated and alternate cycles of 24 hr withdrawals and 1 week of chronic ethanol treatment. The microdialysis technique was used together with high-performance liquid chromatography and electrochemical detection to quantify different amino acids such as aspartate and glutamate. An intraperitoneal administration of acamprosate (400 mg/kg) to naïve rats did not alter aspartate or glutamate levels compared with the saline groups. During the first cycle of ethanol withdrawal, the administration of acamprosate (400 mg/kg, intraperitoneally) 2 hr after the commencement of ethanol withdrawal decreased both aspartate and glutamate microdialysate levels when compared with their respective saline group. Acamprosate administration also significantly decreased glutamate levels during the third withdrawal compared with the saline group, whereas no changes were seen in aspartate levels. The results of this work demonstrate that acamprosate reduced the excitatory amino acid glutamate increase observed during repeated ethanol withdrawal. These effects of acamprosate may provide a protective mechanism against neurotoxicity by reducing excitatory amino acids, particularly glutamate.

Excitatory and inhibitory amino acid changes during repeated episodes of ethanol withdrawal: an in vivo microdialysis study

Changes in amino acid levels in the hippocampus during repeated ethanol withdrawal were studied. Wistar rats were made ethanol-dependent by 4-week vapour inhalation. After this first cycle of chronic ethanol treatment, rats underwent repeated and alternate cycles of 24 h of withdrawal followed by 1 week of chronic ethanol treatment. The microdialysis technique was used together with high-performance liquid chromatography and electrochemical detection to separate and quantify different amino acids such as aspartate, glutamate, arginine, taurine, alanine and γ-aminobutyric acid. During the first cycle of ethanol withdrawal, increases in glutamate, taurine and alanine levels were observed. During the third withdrawal period, further increases were detected in aspartate, glutamate, taurine and alanine in the comparison with levels in the control group. However, the arginine level during the third withdrawal period decreased when compared to that after the first withdrawal period. The results of this study demonstrate that excitatory amino acid levels increased with subsequent withdrawal periods.

At home abroad: identity and power in American foreign policy

The United States has never felt at home abroad. The reason for this unease, even after the terrorist attacks of September 11, 2001, is not frequent threats to American security. It is America's identity. The United States, its citizens believe, is a different country, a New World of divided institutions and individualistic markets surviving in an Old World of nationalistic governments and statist economies. In this Old World, the United States finds no comfort and alternately tries to withdraw from it and reform it. America cycles between ambitious internationalist efforts to impose democracy and world order, and more nationalist appeals to trim multilateral commitments and demand that the European and Japanese allies do more. In At Home Abroad, Henry R. Nau explains that America is still unique but no longer so very different. All the industrial great powers in western Europe (and, arguably, also Japan) are now strong liberal democracies. A powerful and peaceful new world exists beyond America's borders and anchors America's identity, easing its discomfort and ending the cycle of withdrawal and reform. Nau draws on constructivist and realist perspectives to show how relative national identities interact with relative national power to define U.S. national interests. He provides fresh insights for U.S. grand strategy toward various countries. In Europe, the identity and power perspective advocates U.S. support for both NATO expansion to consolidate democratic identities in eastern Europe and concurrent, but separate, great-power cooperation with Russia in the United Nations. In Asia, this perspective recommends a shift of U.S. strategy from bilateralism to concentric multilateralism, starting with an emerging democratic security community among the United States, Japan, South Korea, Australia, New Zealand, India, and Taiwan, and progressively widening this community to include reforming ASEAN states and, if it democratizes, China. In the developing world, Nau's approach calls for balancing U.S. moral (identity) and material (power) commitments, avoiding military intervention for purely moral reasons, as in Somalia, but undertaking such intervention when material threats are immediate, as in Afghanistan, or material and moral stakes coincide, as in Kosovo.