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Alcohol use disorders are modulated by genetic factors, but the identification of specific genes and their concomitant biological changes that are associated with a higher risk for these disorders has proven difficult. Alterations in the sensitivity to the motivational effects of ethanol may be one way by which genes modulate the initiation and escalation of ethanol intake. Rats and mice have been selectively bred for high and low ethanol consumption during adulthood. However, selective breeding programs for ethanol intake have not focused on adolescence. This phase of development is associated with the initiation and escalation of ethanol intake and characterized by an increase in the sensitivity to ethanol's appetitive effects and a decrease in the sensitivity to ethanol's aversive effects compared with adulthood. The present study performed short-term behavioral selection to select rat lines that diverge in the expression of ethanol drinking during adolescence. A progenitor nucleus of Wistar rats (F0) and filial generation 1 (F1), F2, and F3 adolescent rats were derived from parents that were selected for high (STDRHI) and low (STDRLO) ethanol consumption during adolescence and were tested for ethanol intake and responsivity to ethanol's motivational effects. STDRHI rats exhibited significantly greater ethanol intake and preference than STDRLO rats. Compared with STDRLO rats, STDRHI F2 and F3 rats exhibited a blunted response to ethanol in the conditioned taste aversion test. F2 and F3 STDRHI rats but not STDRLO rats exhibited ethanol-induced motor stimulation. STDRHI rats exhibited avoidance of the white compartment of the light-dark box, a reduction of locomotion, and a reduction of saccharin consumption, suggesting an anxiety-prone phenotype. The results suggest that the genetic risk for enhanced ethanol intake during adolescence is associated with lower sensitivity to the aversive effects of ethanol, heightened reactivity to ethanol's stimulating effects, and enhanced innate anxiety.

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BACKGROUND: There are no population studies estimating the burden of alcoholic cerebellar degeneration (ACD). We aimed to assess prevalence and correlates of ACD among chronic alcohol drinkers living in rural Ecuador. METHODS: Characteristics of alcohol intake were evaluated in community-dwelling men aged ≥40years enrolled in the Atahualpa Project. Cerebellar dysfunction evaluation used the Brief Ataxia Rating Scale (BARS). Association between alcohol intake and the BARS was assessed in generalized linear models adjusted for relevant confounders. In subjects who had CT, the relationship between cerebellar atrophy and the BARS was evaluated. RESULTS: Of the 313 men identified during a door-to-door survey, 246 (79%) were enrolled. All admitted continuous drinking for ≥10years. Of these, 41% started drinking below legal age (18years), 72% were current drinkers, and 83% engaged in binge drinking. Average alcohol intake was 330±351g/week. Mean BARS score was 1.4±2 points, with 14.6% (95% C.I.: 10.8%-19.6%) of individuals having ≥4 points and considered to have clinically relevant ACD. The BARS was associated with years of drinking (p=0.036), amount of alcohol intake (p<0.0001), and binge drinking (p=0.026). Predictive models showed significant relationships between BARS score margins and years of drinking and the amount of alcohol intake, independent of other variables. There was no association between cerebellar atrophy on CT and the BARS in 214 participants. CONCLUSIONS: Prevalence of clinically relevant ACD in this population is low. There are both independent and synergistic effects of years of drinking, amount of alcohol intake and binge drinking in the severity of cerebellar dysfunction.

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This study was aimed at exploring the electroencephalographic features associated with alcohol use disorders (AUD) during a resting-state condition, by using quantitative EEG and Functional Connectivity analyses. In addition, we explored whether EEG functional connectivity is associated with trait impulsivity. Absolute and relative powers and Synchronization Likelihood (SL) as a measure of functional connectivity were analyzed in 15 AUD women and fifteen controls matched in age, gender and education. Correlation analysis between self-report impulsivity as measured by the Barratt impulsiveness Scale (BIS-11) and SL values of AUD patients were performed. Our results showed increased absolute and relative beta power in AUD patients compared to matched controls, and reduced functional connectivity in AUD patients predominantly in the beta and alpha bands. Impaired connectivity was distributed at fronto-central and occipito-parietal regions in the alpha band, and over the entire scalp in the beta band. We also found that impaired functional connectivity particularly in alpha band at fronto-central areas was negative correlated with non-planning dimension of impulsivity. These findings suggest that functional brain abnormalities are present in AUD patients and a disruption of resting-state EEG functional connectivity is associated with psychopathological traits of addictive behavior.

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Heightened neural responsiveness of alcoholics to alcohol cues and social emotion may impede sobriety. To test mesocorticolimbic network responsivity, 10 (8 men) alcohol use disorder (AUD) patients sober for 3 weeks to 10 months and 11 (8 men) controls underwent fMRI whilst viewing pictures of alcohol and non-alcohol beverages and of emotional faces (happy, sad, angry). AUD and controls showed similarities in mesocorticolimbic activity: both groups activated fusiform for emotional faces and hippocampal and pallidum regions during alcohol picture processing. In AUD, less fusiform activity to emotional faces and more pallidum activity to alcohol pictures were associated with longer sobriety. Using graph theory-based network efficiency measures to specify the role of the mesocorticolimbic network nodes for emotion and reward in sober AUD revealed that the left hippocampus was less efficiently connected with the other task-activated network regions in AUD than controls when viewing emotional faces, while the pallidum was more efficiently connected when viewing alcohol beverages. Together our findings identified lower occipito-temporal sensitivity to emotional faces and enhanced striatal sensitivity to alcohol stimuli in AUD than controls. Considering the role of the striatum in encoding reward, its activation enhancement with longer sobriety may reflect adaptive neural changes in the first year of drinking cessation and mesocorticolimbic system vulnerability for encoding emotional salience and reward potentially affecting executive control ability and relapse propensity during abstinence.

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Increased reactive oxygen species generation and mitochondrial dysfunction occur during ethanol hangover. The aim of this work was to study the effect of melatonin pretreatment on motor performance and mitochondrial function during ethanol hangover. Male mice received melatonin solution or its vehicle in drinking water during 7 days and i.p. injection with EtOH (3.8 g/kg BW) or saline at the eighth day. Motor performance and mitochondrial function were evaluated at the onset of hangover (6h after injection). Melatonin improved motor coordination in ethanol hangover mice. Malate-glutamate-dependent oxygen uptake was decreased by ethanol hangover treatment and partially prevented by melatonin pretreatment. Melatonin alone induced a decrease of 30% in state 4 succinate-dependent respiratory rate. Also, the activity of the respiratory complexes was decreased in melatonin-pretreated ethanol hangover group. Melatonin pretreatment before the hangover prevented mitochondrial membrane potential collapse and induced a 79% decrement of hydrogen peroxide production as compared with ethanol hangover group. Ethanol hangover induced a 25% decrease in NO production. Melatonin alone and as a pretreatment before ethanol hangover significantly increased NO production by nNOS and iNOS as compared with control groups. No differences were observed in nNOS protein expression, while iNOS expression was increased in the melatonin group. Increased NO production by melatonin could be involved in the decrease of succinate-dependent oxygen consumption and the inhibition of complex IV observed in our study. Melatonin seems to act as an antioxidant agent in the ethanol hangover condition but also exhibited some dual effects related to NO metabolism.

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PURPOSE: Investigate the morphological effects of chronic exposure to tobacco smoke inhalation and alcohol consumption on the lungs and on the growth of rats. METHODS: Sixty male Wistar rats were divided into four groups: control, tobacco, alcohol, tobacco + alcohol, for a period of study 260 days. Morphological analysis was conducted by optical and electron microscopy. Rat growth was investigated by measuring the snout-anus length, body mass index and body weight. RESULTS: The three groups exposed to the drugs presented lower growth and lower weight than the control group. The percentages of alveolitis, bronchiolitis and the mean alveolar diameter were greater, particularly in the groups exposed to tobacco smoke, but were not significantly different from the control group. Electron microscopy revealed more intense apoptotic and degenerative lesions in the smoking group, while degenerative lesions in the lamellar bodies were more intense with the association of both drugs. CONCLUSIONS: This experimental model showed morphological alterations observed by electron microscopy, principally due to tobacco smoke exposure. Alcohol and tobacco hindered the growth of rats, such that tobacco showed a greater effect on body length and alcohol on body weight.(AU)

OBJETIVO: Investigar os efeitos morfológicos da exposição crônica à inalação de fumaça do tabaco e o do consumo de álcool nos pulmões e no crescimento de ratos. MÉTODOS: Sessenta ratos Wistar machos foram distribuídos em quatro grupos: controle, tabaco, álcool e tabaco + álcool, e acompanhados por um período de 260 dias. No final do periodo foi realizada análise morfológica dos pulmões por microscopia óptica e eletrônica. O crescimento dos ratos foi investigado através da medição do comprimento focinho-ânus, peso corporal e índice de massa corporal. RESULTADOS: Os três grupos expostos às drogas apresentaram peso e comprimento significativamente menores que os do grupo controle. As percentagens de bronquiolite e alveolite, e o diâmetro alveolar médio foram maiores nos grupos expostos à fumaça do tabaco, mas sem significancia estatística quando comparadas ao grupo controle. A microscopia eletrônica revelou apoptose mais intensa e lesões degenerativas no grupo de fumantes, enquanto lesões degenerativas nos corpos lamelares foram mais intensas com a associação de ambas as drogas. CONCLUSÕES: Este modelo experimental mostrou alterações morfológicas observadas por microscopia eletrônica, principalmente devido à exposição ao tabaco. Tanto o alcool como o tabaco prejudicaram o crescimento dos animais, o tabaco mostrando um efeito maior sobre o comprimento e o álcool sobre o peso corporal.(AU)

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BACKGROUND: Two of the class I alcohol dehydrogenase (ADH) genes located on chromosome 4 (ADH1B and ADH1C) encode for multiple isozymes that differ in their kinetic properties. At the ADH1B locus, 3 polymorphisms are present (ADH1B(*)1, ADH1B(*)2, ADH1B(*)3). ADH1B(*)2 (found mostly in individuals of East Asian and Jewish descent) and ADH1B(*)3 (found mostly in individuals of African decent) alleles encode for a more active enzyme variants than ADH1B(*)1 and the presence of these alleles has been associated with protection from alcohol dependence. The relationship between these alleles and alcohol-associated phenotypes has not been previously investigated in individuals living in the Caribbean. METHODS: One hundred thirty-three alcohol-dependent individuals of either East Indian or African ancestry and 98 controls matched by age, sex, education, and ethnicity participated in the study. A structured interview [the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA)] was used to gather information on demographics, psychiatric diagnoses, personal drinking, and drug use history. Leukocyte DNA extracted from a blood sample obtained from each participant was genotyped at the ADH1B locus. Serum levels of the liver enzymes alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) as well as the presence of HIV, hepatitis B surface antigen, and antihepatitis C virus antibody were also assayed. The specific aim of the study was to investigate the associations between ADH1B alleles and alcohol dependence, drinking history, and liver function in individuals from the 2 major ethnic groups of Trinidad (individuals of African and East Indian ancestry). RESULTS: Twenty-eight of the Afro-Trinidadian (Afro-TT) participants (41%) and 1 Indo-Trinidadian (Indo-TT) (>1%) had at least 1 ADH1B(*)3 allele and 3 Afro-TT were homozygous for the allele. African participants with at least 1 ADH1B(*)3 allele were found to be significantly less likely to be alcohol dependent (p<0.018), and to have lower alcohol consumption levels (p<0.05). Among those participants who were alcohol dependent, ADH1B(*)3 was associated with significantly higher levels of ALT (p<0.05). CONCLUSIONS: This study suggests, in this sample of Trinidadians, that the ADH1B(*)3 allele is associated with protection from the development of alcoholism but is also associated with enhanced risk for elevated serum ALT levels in those individuals who do become alcohol dependent.

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O uso crônico e abusivo do alcool causa uma ampla variedade de alterações sistemicas, entre elas cardiopatia. A doença alcoolica cardíaca(DAC) apresenta-se como um quadro clínico bastante similiar ao da miocardiopatia dilatada, mas admite-se que as alterações clínicas e histológicas säo mais discretas e aparentemente, possuem certo potencial de regressäo. Neste trabalho foi estudado o caraçäo de 19 alcoolistas autopsiadas na cidade do recife. o grupo controle constatou de doze indivíduos sem historia de alcoolismo. O peso cardíaco do grupo alcoolista foi maior que no grupo controle (299,ñ14,5g vs256,2ñ18,2g), entretanto sem alcançar significância estatística. A espessura da parede e altura das câmeras ventriculares também foram maiores do que no grupo controle, mas apenas a altura do ventrículo direito mostrou uma diferença estatisticamente significante. As alterações histológicas foram represeentadas por fibrose predominantemente perivascular, vacuolizaçäo e acúmulo de lipofuscina em miocardiócitos, além de infiltrado inflamatório mononuclear leve. O dano miocárdico é inespecífico e atribuível aos efeitos tóxicos diretos do álcool onde seus subprodutos, como acetaldeído e acetato

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