Query: Alcohol dependence;Suppression control;Rewards

title: Pavlovian to Instrumental Transfer in Alcohol Dependence: A Pilot Study
abstract: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian to instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT.  Thirty two recently detoxified alcohol dependent patients and 32 age and gender matched healthy controls performed a PIT task with instrumental go/no go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks.  Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression) but there was no group difference in response to appetitive CSs.  The implementation of PIT has favorably robust properties in chronic alcohol dependent patients and in healthy controls. It shows internal consistency between monetary and drug related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT. 2014 S. Karger AG, Basel

title: Upregulation of Voluntary Alcohol Intake, Behavioral Sensitivity to Stress, and Amygdala Crhr1 Expression Following a History of Dependence
abstract: A history of alcohol dependence recruits increased voluntary alcohol intake and sensitivity to stress. Corticotropin releasing hormone (CRH) has been implicated in this transition, but underlying molecular mechanisms remain unclear.  A postdependent state was induced using intermittent alcohol exposure. Experiments were carried out following or =3 weeks of recovery to eliminate contributions of acute withdrawal. Voluntary alcohol consumption was assessed in a two bottle, free choice procedure. Behavioral sensitivity to stress was examined using fear suppression of behavior in a punished drinking (Vogel) conflict test. Effects of forced swim stress on voluntary alcohol intake were examined as a function of exposure history. Expression of Crh, Crhr1, and Crhr2 transcripts was analyzed by in situ hybridization histochemistry.  Alcohol drinking was upregulated long term following a history of dependence. Fear suppression of behavior was selectively potentiated in postdependent animals. This persisted 3 months after alcohol exposure and was reversed by the selective CRH R1 antagonist 3 (4 Chloro 2 morpholin 4 yl thiazol 5 yl) 8 (1 ethylpropyl) 2,6 dimethyl imidazo[1,2 b]pyridazine (MTIP) (10 mg/kg) Forced swim stress increased alcohol intake in postdependent animals but not in control animals. Behavioral changes were paralleled by an upregulation of Crhr1 transcript expression within basolateral (BLA) and medial (MeA) amygdala and Crh messenger RNA (mRNA) in central amygdala (CeA) In contrast, Crhr2 expression was down in the BLA.  Neuroadaptations encompassing amygdala CRH signaling contribute to the behavioral phenotype of postdependent animals.

title: Treatment in hospital for alcohol dependent patients decreases attentional bias
abstract: Previous studies in alcohol dependent patients have shown an attentional bias (AB) under related substance cues, which can lead to relapse. This AB can be evaluated by the alcohol Stroop test (AST) The AST is a modified Stroop task in which participants have to name the color of an alcohol related word or a neutral word. AB is the response time difference between these two types of words. The goal of the current study was to examine modification of AB during specialized hospitalization for alcohol dependence, with the suppression of a training bias that could be present in within subject design.  Individuals with alcohol dependence disorders (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) and admitted for withdrawal in the addiction unit of the University Hospital of Clermont Ferrand (test group, n 42) and persons with no alcohol or psychiatric disorder (control group, n 16) recruited among colleagues and friends of the staff, performed the AST. A subgroup of the test group performed the AST in admission (admission group, n 19) and another subgroup undertook the test immediately before discharge (discharge group, n 23)  Results showed an AB only for patients seen at admission (F[1,55] 3.283, P 0.075) Moreover, we observed that the AB in the admission group (mean 34 ms, standard deviation [SD] 70.06) was greater than the AB in the control group (mean 23 ms, SD 93.42) itself greater than the AB in the discharge group (mean 12 ms, SD 93.55) (t[55] 1.71; P 0.09)  Although the results are preliminary, the present study provides evidence for changes in the AB during alcohol addiction treatment and for the value of these methods to diminish AB during detoxification.

title: Inhibition of Cortical Activity and Apoptosis Caused by Ethanol in Neonatal Rats In Vivo
abstract: Alcohol consumption during pregnancy causes fetal alcohol spectrum disorder, which includes neuroapoptosis and neurobehavioral deficits. The neuroapoptotic effects of alcohol have been hypothesized to involve suppression of brain activity. However, in vitro studies suggest that ethanol acts as a potent stimulant of cortical activity. We explored the effects of alcohol (1 6 g/kg) on electrical activity in the rat somatosensory cortex in vivo at postnatal days P1 23 and compared them with its apoptotic actions. At P4 7, when the peak of alcohol induced apoptosis was observed, alcohol strongly suppressed spontaneous gamma and spindle bursts and almost completely silenced neurons in a dose dependent manner. The dose dependence of suppression of neuronal activity strongly correlated with the alcohol induced neuroapoptosis. Alcohol also profoundly inhibited sensory evoked bursts and suppressed motor activity, a physiological trigger of cortical activity bursts in newborns. The suppressive effects of ethanol on neuronal activity waned during the second and third postnatal weeks, when instead of silencing the cortex, alcohol evoked delta wave electrographic activity. Thus, the effects of alcohol on brain activity are strongly age dependent, and during the first postnatal week alcohol profoundly inhibits brain activity. Our findings suggest that the adverse effects of alcohol in the developing brain involve suppression of neuronal activity.

title: Educational Inequalities in Exit from Paid Employment among Dutch Workers: The Influence of Health, Lifestyle and Work
abstract: Individuals with lower socioeconomic status are at increased risk of involuntary exit from paid employment. To give sound advice for primary prevention in the workforce, insight is needed into the role of mediating factors between socioeconomic status and labour force participation. Therefore, it is aimed to investigate the influence of health status, lifestyle related factors and work characteristics on educational differences in exit from paid employment.  Dutch employees participated in a ten year follow up study during 1999 2008. At baseline, education, self perceived health, lifestyle (smoking, alcohol, sports, BMI) and psychosocial (demands, control, rewards) and physical work characteristics were measured by questionnaire. Employment status was ascertained monthly based on tax records. The relation between education, health, lifestyle, work characteristics and exit from paid employment through disability benefits, unemployment, early retirement and economic inactivity was investigated by competing risks regression analyses. The mediating effects of these factors on educational differences in exit from paid employment were tested using a stepwise approach.  Lower educated workers were more likely to exit paid employment through disability benefits (SHR:1.84) unemployment (SHR:1.74) and economic inactivity (SHR:1.53) but not due to early retirement (SHR:0.92) Poor or moderate health, an unhealthy lifestyle, and unfavourable work characteristics were associated with disability benefits and unemployment, and an unhealthy lifestyle with economic inactivity. Educational differences in disability benefits were explained for 40% by health, 31% by lifestyle, and 12% by work characteristics. For economic inactivity and unemployment, up to 14% and 21% of the educational differences could be explained, particularly by lifestyle related factors.  There are educational differences in exit from paid employment, which are partly mediated by health, lifestyle and work characteristics, particularly for disability benefits. Health promotion and improving working conditions seem important measures to maintain a productive workforce, particularly among workers with a low education.

title: Treatment of alcohol use disorders
abstract: In the treatment of alcohol dependence, Marc Schuckit (Feb 7, p 492) omits baclofen. This is most regrettable for two reasons. First, Schuckit's proposed treatment excludes patients with liver cirrhosis from receiving any anticraving medication. Alcohol intake in patients with cirrhosis is associated with high mortality. With cirrhosis, naltrexone is contraindicated and the safety of acamprosate, topiramate, and disulfi ram has not been tested because these agents undergo extensive liver metabolism. Baclofen is the only anticraving medication shown in a randomised trial to be safe and eff ective at promoting abstinence in patients with cirrhosis. Depriving cirrhosis patients of baclofen would deprive them of the benefi t patients without cirrhosis get from standard anticraving treatment. Second, a new translational model of treatment based on animal studies has been proposed, in which medication induced suppression of craving could translate into eff ortless suppression of dependence in alcohol dependent patients. In animals, baclofen is the only drug that has been shown to suppress the urge to consume alcohol. All other anticraving medications used in the treatment of alcohol dependence only reduce this urge. In alcoholic patients, suppression of dependence through suppression of craving has never been reported with naltrexone, acamprosate, or topiramate despite thousands of patients trialled on these drugs. Baclofen should be off ered to patients with cirrhosis, and craving suppression should be tested in randomised trials.

title: Treatment of alcohol use disorders Authors' reply
abstract: In the treatment of alcohol dependence, Marc Schuckit (Feb 7, p 492) omits baclofen. This is most regrettable for two reasons. First, Schuckit's proposed treatment excludes patients with liver cirrhosis from receiving any anticraving medication. Alcohol intake in patients with cirrhosis is associated with high mortality. With cirrhosis, naltrexone is contraindicated and the safety of acamprosate, topiramate, and disulfi ram has not been tested because these agents undergo extensive liver metabolism. Baclofen is the only anticraving medication shown in a randomised trial to be safe and eff ective at promoting abstinence in patients with cirrhosis. Depriving cirrhosis patients of baclofen would deprive them of the benefi t patients without cirrhosis get from standard anticraving treatment. Second, a new translational model of treatment based on animal studies has been proposed, in which medication induced suppression of craving could translate into eff ortless suppression of dependence in alcohol dependent patients. In animals, baclofen is the only drug that has been shown to suppress the urge to consume alcohol. All other anticraving medications used in the treatment of alcohol dependence only reduce this urge. In alcoholic patients, suppression of dependence through suppression of craving has never been reported with naltrexone, acamprosate, or topiramate despite thousands of patients trialled on these drugs. Baclofen should be off ered to patients with cirrhosis, and craving suppression should be tested in randomised trials.

title: Family management risk and protective factors for adolescent substance use in South Africa
abstract: BackgroundAn increasingly recognised prevention approach for substance use entails a reduction in risk factors, and the enhancement of promotive, or protective factors in individuals and the environment surrounding them during their growth and development.MethodsThis exploratory study evaluated the effect of potential risk and protective factors associated with family management relating to adolescent substance use in South Africa. Exploratory analysis and cumulative odds ordinal logistic regression modelling was performed on the data, while controlling for the influence of demographic and socio economic characteristics on adolescent substance use.ResultsThe most frequently used substances were cannabis, followed by other illicit substances and alcohol in decreasing order of use intensity. The specific protective, or risk effect of family management factors, varied according to substance. Risk factors associated with demographic and socio economic factors included being male, of a younger age, lower education grades, of a coloured ethnicity, adolescents from divorced parents, and unemployed or fully employed mothers. Several family management factors, categorised as parental monitoring, discipline, behavioural control and rewards, demonstrated either risk or protective effects on adolescent substance use.ConclusionsThis exploratory study demonstrated that various risk and protective factors associated with family management may affect adolescent substance use. Interaction amongst risk or protective factors, as well as the type of substance, should be considered when further considering interventions based on these risk or protective factors.

title: Associacao entre uso de alcool em individuos com AIDS e adesao ao tratamento antirretroviral: uma revisao da literatura
abstract: The purpose of this work was to make a systematic review of the literature, using the MedLine data basis, about the alcohol usage/abuse/dependence as a risk factor to the adherence reduction, the viral load reduction or even a worse clinical outcome in HIV patients in the usage of highly active antiretroviral therapy (HAART) METHOD: It was made a systematic research in the MedLine data basis using the words: "HAART" "adherence" and "alcohol" with the purpose of finding articles about the themes: evaluations or association between the alcohol usage/abuse/dependence and adherence/suppression of the viral load/clinical outcome in HIV patients in the usage of antiretroviral therapy.  The search found 65 articles. However, only 21 of this achieved the pre established criteria and have been selected. It was found a positive association among the usage/abuse/dependence of the alcohol and the low adherence/low viral load suppression/worse clinical outcome in 18 (85,7% of the articles.  We could conclude that the alcohol usage/abuse/dependence is a risk factor to the low adherence/low viral load suppression/worse clinical outcome in HIV patients in the usage of HAART.

title: Baclofen overdose/withdrawal
abstract: Various toxicities: case report A 33 years old woman received off label treatment with baclofen and developed withdrawal syndrome following baclofen overdose [route and duration of treatment to reaction onsets not stated] The woman, who had a history of alcohol dependence, was admitted to the emergency room for fatigue, vomiting and neurological disorders. A clinical examination showed acute neurological disorders including confusion, extremity and head tremors. Subsequently, she was transferred to the nephrology acute care unit. On the 4th day, her condition worsened. She was febrile, tachycardic, icteric, tachypneic, oliguric with mottling at the level of lower limbs. She had an extracellular dehydration and her mean arterial pressure was above 70 mmHg. The Glasgow Coma Scale score was 13. Subsequently, confusion was diagnosed with a spatial disorientation. Her pupils were dilated and reactive to light. She did not exhibit sensory or motor deficit and the plantar response was inflexion. She had a global increased muscle tone, predominating at the level of head rotated to the left side and upper limbs. The Laboratory values revealed a rhabdomyolysis with a CPK at 6185 UI/L, an AST at 215 UI/L, an ALT at 104 UI/ L, a GGT at 1485 UI/L, an alkaline phosphatase at 258 UI/L, a hyperbillirubinaemia at 61 mmol/L. Therefore, she was referred to the ICU. A transthoracic ECG revealed signs suggesting a preload dependence. Subsequently, her family mentioned that she had received baclofen up to 560 mg/day for alcohol dependence suppression. The treatment was initially prescribed by a psychiatrist but later, she developed self medication. She abruptly discontinued her baclofen treatment due to an acute gastroenteritis. The woman was immediately treated with fluid resuscitation with crystalloids. The baclofen was reintroduced at 60 mg/d, and clonidine plus benzodiazepine were also given for her withdrawal symptoms. After 2 days in the ICU, blood sample revealed an increase of rhabdomyolysis. The hyperthermia and an increased muscle tone were also persistent. In the following days, her all biological variables became normal and she recovered fully. Since 2008, off label baclofen is prescribed for alcohol use disorders." "We report here a case of baclofen withdrawal syndrome secondary to an abrupt cessation of very high dose treatment for alcohol use disorders, mimicking neuroleptic malignant syndrome in a 33 years old patient."