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Alcohol Addiction (alcohol + addiction)
Selected AbstractsInvolvement of Acetaldehyde in Alcohol AddictionALCOHOLISM, Issue 1 2002William J. McBride This article presents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizers and chairs were William J. McBride and Ting-Kai Li. The presentations were (1) Metabolism of ethanol in the brain and the behavioral consequences, by Richard A. Deitrich and Sergey Zimatkin; (2) Catalase production of acetaldehyde as a possible mediator of the psychopharmacological effects of ethanol, by Brian R. Smith; (3) The reinforcing actions of acetaldehyde in the ventral tegmental area, by Zachary A. Rodd-Henricks; and (4) Salsolinol and alcohol addiction, by William J. McBride. [source] Genetic Determinants of Alcohol Addiction and Metabolism: A Survey in ItalyALCOHOLISM, Issue 2 2001Roberta Pastorelli Background: Although multiple genes are involved in alcoholism and can contribute differently to the risk of dependence and liver damage, no studies have investigated susceptibility to addiction in combination with susceptibility to liver damage due to differences in ethanol metabolism. Methods: We evaluated the role of three polymorphic genes related to alcohol metabolism (CYP2E1) and, possibly, dependence (DRD2 and SLC6A4 promoter) in a series of 60 alcoholics admitted to a specialized referral center in Florence, Italy. Eighteen had a diagnosis of liver cirrhosis. A control series of 64 blood donors were identified at the same hospital. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism methods. Results: No difference was found in the frequency of the CYP2E 1 Rsa I c2 allele (2.5% among alcoholics and 4.7% among controls) and the Dra I C allele (6.7% and 10.1%). Similarly, no difference was found in the frequency of the DRD2 A1 allele (15.8% and 13.3%) and the B1 allele (10.8% and 8.6%). The proportion of controls with a combined B1 genotype (B1/B1 or B1/B2) was significantly associated with smoking (p= 0.03). The distribution of the S and L allele of the SLC6A4 gene was similar in the two groups, with 15% and 14%, respectively, homozygous S/S carriers. A significant association, however, emerged in the group of alcoholics, with a five times higher risk for S/S carriers of developing cirrhosis (p < 0.05). This association with liver persisted even after exclusion of the subgrouped of 10 hepatitis C virus positive alcoholics. Conclusions: Overall, our results provided no evidence of an increased susceptibility to develop alcoholism that was associated with the three genotypes investigated, either alone or in combination. An increased risk of developing liver cirrhosis for S/S homozygous carriers among alcohol-dependent patients was observed for the first time. [source] Mortality risk up to 25 years after initiation of treatment among 420 Swedish women with alcohol addictionADDICTION, Issue 3 2009Brit Haver ABSTRACT Aims Women treated for alcohol addiction have mortality rates three to five times those of women from the general population (GP). However, these figures may be inflated because socially disadvantaged women with advanced drinking careers are over-represented in previous studies. Our aim was to study the long-term mortality of socially relatively well-functioning patients coming to their first treatment, compared to matched GP controls. Design The mortality rates and causes of death were compared between patients and their matched GP controls, using data from the Causes of Death Register throughout the follow-up period (0,25 years). Setting A specialized treatment programme for women only, called ,Early treatment for Women with Alcohol Addiction' (EWA) at the Karolinska Hospital, Stockholm, Sweden. Participants Subjects (n = 420) receiving their first treatment at the EWA programme, compared to a group of matched GP women (n = 2037). Findings The women patients had significantly higher mortality than matched GP controls throughout the whole follow-up period, with a relative risk of 2.4. However, the younger women had four times higher mortality than their matched controls. The peak of deaths occurred during the first 5 years, and alcohol-related causes of death were highly over-represented, as were uncertain suicides and accidents. Conclusions First-time-treated women with alcohol addiction have a substantially lower mortality than reported previously from clinical samples, except for the youngest group. Our figures were corrected for confounding factors such as socio-demographic status. We believe our results could apply to broader groups of heavy drinking women, inside or outside specialized treatment settings. [source] Interactive Effects of Cumulative Stress and Impulsivity on Alcohol ConsumptionALCOHOLISM, Issue 8 2010Fox Helen C. Background:, Alcohol addiction may reflect adaptations to stress, reward, and regulatory brain systems. While extensive research has identified both stress and impulsivity as independent risk factors for drinking, few studies have assessed the interactive relationship between stress and impulsivity in terms of hazardous drinking within a community sample of regular drinkers. Methods:, One hundred and thirty regular drinkers (56M/74F) from the local community were assessed for hazardous and harmful patterns of alcohol consumption using the Alcohol Use Disorders Identification Test (AUDIT). All participants were also administered the Barratt Impulsiveness Scale (BIS-11) as a measure of trait impulsivity and the Cumulative Stress/Adversity Checklist (CSC) as a comprehensive measure of cumulative adverse life events. Standard multiple regression models were used to ascertain the independent and interactive nature of both overall stress and impulsivity as well as specific types of stress and impulsivity on hazardous and harmful drinking. Results:, Recent life stress, cumulative traumatic stress, overall impulsivity, and nonplanning-related impulsivity as well as cognitive and motor-related impulsivity were all independently predictive of AUDIT scores. However, the interaction between cumulative stress and total impulsivity scores accounted for a significant amount of the variance, indicating that a high to moderate number of adverse events and a high trait impulsivity rating interacted to affect greater AUDIT scores. The subscale of cumulative life trauma accounted for the most variance in AUDIT scores among the stress and impulsivity subscales. Conclusions:, Findings highlight the interactive relationship between stress and impulsivity with regard to hazardous drinking. The specific importance of cumulative traumatic stress as a marker for problem drinking is also discussed. [source] Altered Motor Cortex Excitability to Magnetic Stimulation in Alcohol Withdrawal SyndromeALCOHOLISM, Issue 4 2010Raffaele Nardone Background:, Alcohol addiction is a complex brain disease caused by alterations in crucial neurotransmitter systems, including gamma-aminobutyric acid (GABA) and glutamate. These disturbances could be revealed by changes in cortical excitability parameters, as assessed by transcranial magnetic stimulation (TMS). This study was aimed to further investigate the complex pathophysiology of alcohol withdrawal syndrome (AWS). Methods:, Motor cortex excitability was examined in 13 subjects with AWS in a mild predelirial state, in 12 chronic alcoholics and in 15 age-matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, short latency intracortical inhibition (SICI), and intracortical facilitation (ICF) to paired TMS were examined. Results:, Intracortical facilitation was significantly increased in the AWS patients when compared with the chronic alcoholics and the control subjects. The other TMS parameters did not differ significantly from the controls. Administration of a single oral dose of the glutamatergic antagonist riluzole in a subgroup of 8 patients significantly reduced ICF; motor threshold and SICI were not affected by riluzole. Conclusion:, Transcranial magnetic stimulation shows a selective increase in intracortical facilitation after ethanol withdrawal. Our findings support the theory that altered glutamatergic receptor function plays an important role in the pathogenesis of human alcohol withdrawal. This study provides further physiological evidence that antiglutamatergic approaches represent an efficacious alternative for treating alcohol withdrawal symptoms. [source] Mortality risk up to 25 years after initiation of treatment among 420 Swedish women with alcohol addictionADDICTION, Issue 3 2009Brit Haver ABSTRACT Aims Women treated for alcohol addiction have mortality rates three to five times those of women from the general population (GP). However, these figures may be inflated because socially disadvantaged women with advanced drinking careers are over-represented in previous studies. Our aim was to study the long-term mortality of socially relatively well-functioning patients coming to their first treatment, compared to matched GP controls. Design The mortality rates and causes of death were compared between patients and their matched GP controls, using data from the Causes of Death Register throughout the follow-up period (0,25 years). Setting A specialized treatment programme for women only, called ,Early treatment for Women with Alcohol Addiction' (EWA) at the Karolinska Hospital, Stockholm, Sweden. Participants Subjects (n = 420) receiving their first treatment at the EWA programme, compared to a group of matched GP women (n = 2037). Findings The women patients had significantly higher mortality than matched GP controls throughout the whole follow-up period, with a relative risk of 2.4. However, the younger women had four times higher mortality than their matched controls. The peak of deaths occurred during the first 5 years, and alcohol-related causes of death were highly over-represented, as were uncertain suicides and accidents. Conclusions First-time-treated women with alcohol addiction have a substantially lower mortality than reported previously from clinical samples, except for the youngest group. Our figures were corrected for confounding factors such as socio-demographic status. We believe our results could apply to broader groups of heavy drinking women, inside or outside specialized treatment settings. [source] REVIEW: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?ADDICTION BIOLOGY, Issue 2 2010Markus Heilig ABSTRACT The role of withdrawal-related phenomena in the development and maintenance of alcohol addiction remains under debate. A ,self-medication' framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol-dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that in most patients, these symptoms abate over 3,6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: (1) are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence?; (2) is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal?; and (3) to what extent is susceptibility to negative affect that persists into protracted abstinence heritable? [source] Peptide signaling paths related to intoxication, memory and addictionADDICTION BIOLOGY, Issue 3 2000William E. M. Lands Many peptides bind to G protein-coupled receptors and activate intracellular signaling paths for adaptive cellular responses. The components of these paths can be affected by signals from other neurotransmitters to produce overall integrated results not easily predicted from customary a priori considerations. This intracellular cross-talk among signaling paths provides a "filter" through which long-term tonic signals affect short-term phasic signals as they progress toward the nucleus and induce long-term adaptation of gene expression which provide enduring attributes of acquired memories and addictions. Peptides of the PACAP family provide intracellular signaling that involves kinases, scaffolding interactions, Ca2 + mobilization, and gene expression to facilitate development of tolerance to alcohol and development of associative memories. The peptide-induced enhancement of NMDA receptor responses to extracellular glutamate also may increase behavioral sensitization to the low doses of alcohol that occur at the onset of each bout of drinking. Because many gene products participate in each signaling path, each behavioral response to alcohol is a polygenic process of many steps with no single gene product sufficient to interpret fully the adaptive response to alcohol. Different susceptibility of individuals to alcohol addiction may be a cumulative result of small differences among the many signaling components. Understanding this network of signals may help interpret future "magic bullets" proposed to treat addiction. [source] Rational alcohol addiction: evidence from the Russian longitudinal monitoring surveyHEALTH ECONOMICS, Issue 9 2006Badi H. Baltagi Abstract Alcohol consumption in Russia is legendary and has been reported to be the third leading cause of death in the former Soviet Union after heart disease and cancer. Are Russian alcohol consumers rational addicts? This paper uses eight rounds of a nationally representative Russian survey spanning the period 1994,2003 to estimate a rational addiction (RA) model for alcohol consumption. This is done in a panel data setting as well as on a wave-by-wave basis. The profile of the Russian drinker finds a huge difference between males and females and the model is estimated by gender. We do not find support for the RA model in Russia for women. For men, although we find that some implications of the RA model are satisfied, we fail to endorse the model empirically on grounds of implausible negative estimates of the discount rate. Copyright © 2006 John Wiley & Sons, Ltd. [source] Sex Differences in Salivary Cortisol Levels Following Naltrexone Administration,JOURNAL OF APPLIED BIOBEHAVIORAL RESEARCH, Issue 2 2000Laura Cousino Klein Effects of endogenous opioid peptide blockade by naltrexone on salivary Cortisol levels were examined in healthy men (n= 8) and women (n= 6). Participants received naltrexone (100 mg) during one laboratory session and a placebo pill during another session. Drug order was counterbalanced across participants. Saliva samples were collected 24 hr after each pill was administered. Among women, salivary Cortisol levels significantly increased following naltrexone administration compared with a placebo pill. Naltrexone administration did not alter salivary Cortisol levels in men. Results suggest sex differences in neuroendocrine sensitivity to opioid blockade, a finding that may hold significance with regard to the treatment of alcohol addiction with naltrexone. [source] Neuropeptide S Receptor Gene Expression in Alcohol Withdrawal and Protracted Abstinence in Postdependent RatsALCOHOLISM, Issue 1 2010Barbara Ruggeri Background:, Alcoholism is a chronic disease characterized by frequent intoxications followed by withdrawal episodes and relapse to alcohol use. Neuroplastic changes associated with these intoxication and withdrawal cycles are thought to play a key role in disease progression. Recently, it has been shown that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system, facilitates relapse to alcohol seeking in laboratory animals. Given that a history of ethanol intoxication may increase vulnerability to alcohol addiction, we sought to determine whether NPS receptor (NPSR) gene expression is altered during withdrawal. Methods:, Rats were subjected to 1 week of intoxication by oral alcohol administration. NPSR gene expression was analyzed by in situ hybridization in rats 12 hours and 7 days after the last alcohol administration. To investigate the functional significance of NPSR system adaptation following protracted withdrawal 7 days after intoxication, we tested the anxiolytic-like properties of NPS in nondependent and postdependent rats using the shock probe defensive burying test (DB). Results:, At both time points, increased NPSR gene expression was observed in several brain areas, including the endopiriform nucleus, the motor cortex, and the medial amygdaloid nucleus. Moderate increases in gene expression were also found in the lateral hypothalamus, paraventricular nucleus, basolateral and central amygdala. Differences from control animals were more pronounced after 7 days of abstinence. The upregulation of the NPSR system at this time point was confirmed by functional data indicating that intracerebroventricular (ICV) NPS administration (0.0, 0.3, and 0.1 nmol/rat) elicits more pronounced anxiolytic effects in postdependent animals than in controls subjected to the electric shock probe DB test. Conclusions:, Neuropeptide S receptor mRNA expression is increased in different brain areas of postdependent rats; as shown in the DB test, this expression change is functionally relevant. [source] Modulation of Brain Endocannabinoid Levels by Voluntary Alcohol Consumption in Alcohol-Preferring AA RatsALCOHOLISM, Issue 10 2009Hanna Malinen Background:, The central nervous system cannabinoid CB1 receptors have been implicated in regulation of alcohol consumption. Less data are available on the role of the endogenous ligands for these receptors, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in alcohol-related behaviors. The purpose of this study was to assess the effects of voluntary alcohol consumption on the levels of these endocannabinoids in key brain areas mediating alcohol reinforcement. Methods:, Female and male alcohol-preferring AA (Alko, Alcohol) rats were trained to drink 10% (v/v) alcohol during 90-min limited access sessions every second day. Following establishment of stable alcohol drinking, half of the subjects were killed immediately before the daily alcohol access ("pre-session" group), while the other half was killed after the drinking session ("post-session" group). A separate control group consisted of water-drinking rats. AEA and 2-AG levels were measured from prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), amygdala, and hippocampus using liquid chromatography,tandem mass spectrometry (LC/MS/MS). Results:, Voluntary alcohol drinking caused widespread alterations in the levels of both AEA and 2-AG. Compared to the water group, increased AEA levels were seen in the pre-session group, but they were decreased immediately following limited access drinking in the female AA rats. Also 2-AG levels were significantly elevated after long alcohol exposure, and an additional increase was found after limited access drinking in PFC. In males, however, the only alterations caused by alcohol drinking were significantly elevated AEA levels in NAc and CPu in the post-session group. No changes were seen in the levels of 2-AG. Conclusions:, These results demonstrate that voluntary alcohol drinking modulates the levels of endocannabinoids in several brain areas implicated in alcohol reinforcement. AEA and 2-AG were differentially affected, suggesting that they could have partially separate modulatory roles. Alterations were more widespread in females than males, possibly reflecting their higher alcohol intake. Taken together, alcohol-induced release of endocannabinoids may have an important role in alcohol reinforcement and development of alcohol addiction. [source] Alcohol-Induced Tolerance and Physical Dependence in Mice With Ethanol Insensitive ,1 GABAA ReceptorsALCOHOLISM, Issue 2 2009David F. Werner Background:, Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, ,-aminobutyric acid type A receptors (GABAA -Rs) have been extensively implicated in ethanol action. The ,1 GABAA -R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that ,1-GABAA -Rs mediate in part these effects of ethanol. Methods:, Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin (KI) mice that have ethanol-insensitive ,1 GABAA -Rs and wildtype (WT) controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex (LORR) assays. Chronic tolerance was assessed on the LORR, fixed speed rotarod, hypothermia, and radiant tail-flick assays following 10 consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess ,1 protein levels. Results:, Compared with controls, KI mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between WT and KI mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in ,1 protein levels, but KIs did not. Conclusions:, We conclude that ,1-GABAA -Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on ,1-containing GABAA -Rs. [source] Cellular Adaptation to Chronic Ethanol Results in Altered Compartmentalization and Function of the Scaffolding Protein RACK1ALCOHOLISM, Issue 10 2003Alicia J. Vagts Background: Previously, we found that acute ethanol induces the translocation of the scaffolding protein RACK1 to the nucleus. Recently, we found that nuclear RACK1 mediates acute ethanol induction of immediate early gene c-fos expression. Alterations in gene expression are thought to lead to long-term changes that ultimately contribute to the development of alcohol addiction and toxicity. Therefore, we sought to determine the effects of chronic exposure of cells to ethanol on the cellular compartmentalization of RACK1 and on c-fos messenger RNA (mRNA) and protein expression. Methods: Rat C6 glioma cells were used as the cell culture model. Immunohistochemistry was implemented to visualize the localization of RACK1 and to monitor the protein level of c-fos. Reverse-transcription polymerase chain reaction was used to measure c- fos mRNA levels. The Tat-protein transduction method was used to transduce recombinant Tat-RACK1 into cells as previously described. Results: Chronic exposure of cells to 200 mM ethanol for 24 and 48 hr resulted in the gradual re-distribution of RACK1 out of the nucleus. It is interesting to note that acute ethanol re-challenge immediately after chronic treatment did not result in RACK1 translocation to the nucleus, and nuclear compartmentalization of RACK1 in response to acute ethanol was detected only after 24 hr of withdrawal. Similar patterns were obtained for c-fos expression. Chronic exposure to ethanol did not result in an increase in mRNA or protein levels of c-fos. Furthermore, acute ethanol exposure did not increase c-fos protein levels in cells that were first treated chronically with ethanol. However, transduction of exogenous RACK1 expressed as a Tat-fusion protein was able to rescue c- fos mRNA expression after chronic ethanol exposure. Conclusions: Our data suggest that RACK1 nuclear compartmentalization and ethanol-induced c-fos expression are transient and are desensitized to ethanol during prolonged exposure to high concentrations. The desensitization is temporary, and RACK1 can respond to acute ethanol treatment after a 24-hr withdrawal period. Our data further suggest that the altered compartmentalization of RACK1 leads to differences in c-fos expression upon acute or chronic exposure to ethanol. In summary, RACK1 is an important molecular mediator of the acute and chronic actions of ethanol on the expression of c-fos. These findings could have implications for the molecular signaling pathways leading to pathologic states associated with alcoholism, including toxicity. [source] Involvement of Acetaldehyde in Alcohol AddictionALCOHOLISM, Issue 1 2002William J. McBride This article presents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizers and chairs were William J. McBride and Ting-Kai Li. The presentations were (1) Metabolism of ethanol in the brain and the behavioral consequences, by Richard A. Deitrich and Sergey Zimatkin; (2) Catalase production of acetaldehyde as a possible mediator of the psychopharmacological effects of ethanol, by Brian R. Smith; (3) The reinforcing actions of acetaldehyde in the ventral tegmental area, by Zachary A. Rodd-Henricks; and (4) Salsolinol and alcohol addiction, by William J. McBride. [source] Factors associated with trauma and posttraumatic stress disorder among homeless youth in three U.S. cities: The importance of transience,JOURNAL OF TRAUMATIC STRESS, Issue 1 2010Kimberly Bender Homeless youth experience disproportionately high rates of trauma and posttraumatic stress disorder (PTSD). This study examined correlates of trauma and PTSD among homeless youth with a focus on the impact of homeless culture, substance addiction, and mental health challenges. Homeless youth (N = 146) from Los Angeles, California, Denver, Colorado, and St. Louis, Missouri, were recruited from organizations providing services to homeless youth using comparable methods. Results indicate that 57% of respondents had experienced a traumatic event and 24% met criteria for PTSD. A multinomial logistic regression model revealed greater transience, alcohol addiction, mania, and lower self-efficacy predicted PTSD whereas trauma exposure was associated with alcohol addiction only. Findings have implications for screening and intervening with traumatized homeless youth across service settings. [source] Interpreting the significance of drinking by alcohol-dependent liver transplant patients: Fostering candor is the key to recoveryLIVER TRANSPLANTATION, Issue 6 2000Robert M. Weinrieb Few studies have examined the value of treating alcohol addiction either before or after liver transplantation. Nevertheless, most liver transplant programs and many insurance companies require 6 months to 1 year of abstinence from alcohol as a condition of eligibility for liver transplantation (the 6-month rule). We believe there are potentially harsh clinical consequences to the implementation of this rule. For example, the natural history of alcohol use disorders often involves brief fallbacks to drinking ("slips"), but when alcoholic liver transplant candidates slip, most are removed from consideration for transplantation or are required to accrue another 6 months of sobriety. Because there is no alternative treatment to liver transplantation for most patients with end-stage liver disease, the 6-month rule could be lethal in some circumstances. In this review, we survey the literature concerning the ability of the 6-month rule to predict drinking by alcoholic patients who undergo liver transplantation and examine its impact on the health consequences of drinking before and after liver transplantation. We believe that fostering candor between the alcoholic patient and the transplant team is the key to recovery from alcoholism. We conclude that it is unethical to force alcoholic liver patients who have resumed alcohol use while waiting for or after transplantation to choose between hiding their drinking to remain suitable candidates for transplantation or risk death by asking for treatment of alcoholism. Consequently, we advocate a flexible approach to clinical decision making for the transplant professional caring for an alcoholic patient who has resumed drinking and provide specific guidelines for patient management. [source] | |||||||||||||