Similar ethanol drinking in adolescent and adult C57BL/6J mice after chronic ethanol exposure and withdrawal

BACKGROUND: Increasing evidence shows that excessive alcohol consumption during adolescence increases vulnerability to alcohol use disorders in adulthood. The aim of this study was to examine differences between adolescent and adult C57BL/6J mice in drinking behavior and blood ethanol (EtOH) concentrations (BECs) after chronic EtOH exposure and withdrawal. METHODS: Male adolescent (PND = 28 to 30) and adult (PND = 70) C57BL/6J mice were allowed to consume EtOH in a 2-bottle choice paradigm (15% EtOH vs. water) for 3 weeks (Baseline drinking, Test 1, and Test 2), which were interspersed with 2 cycles (Cycles I and II) of chronic EtOH vapor or air inhalation (16 hours) and withdrawal (8 hours). BECs were determined during both cycles. RESULTS: Chronic EtOH exposure led to increased EtOH intake during Test 1 and Test 2 in both adolescent and adult mice compared with air-exposed controls, and no differences between age groups were observed. During Cycle I adult mice showed higher BECs compared with adolescents. During Cycle II, BECs were lower in adult mice as compared to Cycle I, and BECs in adolescent mice did not change between the 2 cycles. CONCLUSIONS: Chronic EtOH exposure followed by withdrawal periods increases EtOH consumption similarly in both adolescent and adult mice, despite differences in BECs

The role of drinking restraint in alcohol dependence: validation of the temptation and restraint inventory in an alcohol dependent sample

Objective: The Temptation and Restraint Inventory (TRI) is commonly used to measure drinking restraint in relation to problem drinking behavior. However, as yet the TRI has not been validated in a clinical group with alcohol dependence. Method: Male (n = 111) and female (n = 57) inpatients with DSM-IV diagnosed alcohol dependence completed the TRI and measures of problem drinking severity, including the Alcohol Dependence Scale and the quantity, frequency and week total of alcohol consumed. Results: The factor structure of the TRI was replicated in the alcohol dependent sample. Cognitive Emotional Preoccupation (CEP), one of the two higher order factors of the TRI, demonstrated sound predictive power toward all dependence severity indices. The other higher order factor, Cognitive Behavioral Control (CBC), was related to frequency of drinking. There was limited support for the CEP/CBC interactional model of drinking restraint. Conclusions: Although the construct validity of the TRI was sound, the measure appears more useful in understanding the development, maintenance and severity of alcohol-related problems in nondependent drinkers. The TRI may show promise in detecting either continuous drinking or heavy episodic type dependent drinkers.

The relationship between personality and drinking restraint in an alcohol dependent sample

Consistent relationships have been demonstrated between problem drinking and certain personality characteristics. A contemporary cognitive model of alcohol misuse, drinking restraint, has recently shown promise in furthering our understanding of problematic drinking. This study examined the potential association between drinking restraint and personality characteristics in 168 alcohol dependent inpatients. Subjects completed the short-scale Revised Eysenck Personality Scales (EPS-R; Eysenck, Eysenck, & Barrett, 1985), Temptation and Restraint Inventory (TRI; Collins & Lapp, 1992), Alcohol Dependence Scale (ADS; Skinner & Allen, 1982) and drinking measures including quantity, frequency and weekly drinking total. Results indicated that although there was some conceptual overlap between drinking restraint and personality factors, the TRI had a unique relationship with indices of problem drinking once personality factors were taken into account. This indicates that restrained drinking and personality, although related, are discrete constructs. While restrained drinking may aid in the understanding of current drinking behavior, personality characteristics appear to contribute to the etiology and maintenance of drinking problems. (c) 2005 Elsevier Ltd. All rights reserved.

A prospective study of personality features predictive of early adolescent alcohol misuse

Personality factors implicated in alcohol misuse have been extensively investigated in adult populations. Fewer studies have clarified the robustness of personality dimensions in predicting early onset alcohol misuse in adolescence. The aim of this study was to examine the predictive utility of two prominent models of personality (Cloninger, 1987; Eysenck & Eysenck, 1975) in emergent alcohol misuse in adolescence. One hundred and 92 secondary school students (mean age = 13.8 years, SD = 0.5) were administered measures of personality (Revised Junior Eysenck Personality Questionnaire – abbreviated; Temperament scale of Junior Temperament and Character Inventory) and drinking behavior (quantity and frequency of consumption, Alcohol Use Disorders Identification Test) at Time 1. At 12-month follow-up, 170 students (88.5%) were retained. Hierarchical multiple regressions revealed the dimensions of psychoticism, extraversion, and Novelty-Seeking to be the most powerful predictors of future alcohol misuse in adolescents. Results provide support for the etiological relevance of these dimensions in the development of early onset alcohol misuse. Findings can be used to develop early intervention programs that target personality risk factors for alcohol misuse in high-risk youth.

Negative mood, implicit alcohol-related memory, and alcohol use in young adults: The moderating effect of alcohol expectancy

Objective Alcohol-related implicit (preconscious) cognitive processes are established and unique predictors of alcohol use, but most research in this area has focused on alcohol-related implicit cognition and anxiety. This study extends this work into the area of depressed mood by testing a cognitive model that combines traditional explicit (conscious and considered) beliefs, implicit alcohol-related memory associations (AMAs), and self-reported drinking behavior. Method Using a sample of 106 university students, depressed mood was manipulated using a musical mood induction procedure immediately prior to completion of implicit then explicit alcohol-related cognition measures. A bootstrapped two-group (weak/strong expectancies of negative affect and tension reduction) structural equation model was used to examine how mood changes and alcohol-related memory associations varied across groups. Results Expectancies of negative affect moderated the association of depressed mood and AMAs, but there was no such association for tension reduction expectancy. Conclusion Subtle mood changes may unconsciously trigger alcohol-related memories in vulnerable individuals. Results have implications for addressing subtle fluctuations in depressed mood among young adults at risk of alcohol problems.

The α5 neuronal nicotinic acetylcholine receptor subunits plays an important role in the sedative effects of ethanol but does not modulate consumption in mice

Alcohol use disorders (AUDs) are a major public health problem, and the few treatment options available to those seeking treatment offer only modest success rates. There remains a need to identify novel targets for the treatment of AUDs. The neuronal nicotinic acetylcholine receptors (nAChRs) represent a potential therapeutic target in the brain, as recent human genetic studies have implicated gene variants in the α5 nAChR subunit as high risk factors for developing alcohol dependence. Here, we evaluate the role of 5* nAChR for ethanol-mediated behaviors using α5+/+ and α5-/- mice. We characterized the effect of hypnotic doses of ethanol and investigated drinking behavior using an adapted Drinking-in-the Dark (DID) paradigm that has been shown to induce high ethanol consumption in mice. We found the α5 subunit to be critical in mediating the sedative effects of ethanol. The α5-/- mice showed slower recovery from ethanol-induced sleep, as measured by loss of righting reflex. Additionally the α5-/- mice showed enhanced impairment to ethanol-induced ataxia. We found the initial sensitivity to ethanol and ethanol metabolism to be similar in both α5+/+ and α5-/- mice. Hence the enhanced sedation is likely due to a difference in the acute tolerance of ethanol in mice deficient of the α5 subunit. However the α5 subunit did not play a role in ethanol consumption for ethanol concentrations ranging from 5% to 30% in the DID paradigm. Additionally, varenicline (Chantix®) was effective in reducing ethanol intake in α5-/- mice. Together, our data suggest that the α5 nAChR subunit is important for the sedative hypnotic doses of ethanol but does not play a role in ethanol consumption. Varenicline can be a treatment option even when there is loss of function of the α5 nAChR subunit.

Effect of the increase in "alcopops" tax on alcohol-related harms in young people : a controlled interrupted time series

Objective: To measure alcohol-related harms to the health of young people presenting to emergency departments (EDs) of Gold Coast public hospitals before and after the increase in the federal government "alcopops" tax in 2008. Design, setting and participants: Interrupted time series analysis over 5 years (28 April 2005 to 27 April 2010) of 15-29-year-olds presenting to EDs with alcohol-related harms compared with presentations of selected control groups. Main outcome measures: Proportion of 15-29-year-olds presenting to EDs with alcohol-related harms compared with (i) 30-49-year-olds with alcohol-related harms, (ii)15-29-year-olds with asthma or appendicitis, and (iii) 15-29-yearolds with any non-alcohol and non-injury related ED presentation. Results: Over a third of 15-29-year-olds presented to ED with alcohol-related conditions, as opposed to around a quarter for all other age groups. There was no significant decrease in alcohol-related ED presentations of 15-29-year-olds compared with any of the control groups after the increase in the tax. We found similar results for males and females, narrow and broad definitions of alcoholrelated harms, under-19s, and visitors to and residents of the Gold Coast. Conclusions: The increase in the tax on al copops was not associated with any reduction in alcohol-related harms in this population in a unique tourist and holiday region. A more comprehensive approach to reducing alcohol harms in young people is needed.

Good choices, great future : an applied theatre prevention program to reduce alcohol-related risky behaviours during Schoolies

Introduction and Aims. The contextual and temporal factors of post-school celebratory events ('Schoolies') place young people at elevated risk of excessive drinking compared with other social occasions. This study investigates the impact of an applied theatre prevention program 'Choices' in reducing the risk of drinking and other risk behaviours during Schoolies celebrations. Design and Methods. Choices was delivered in the last term of Year 12 across 28 North Queensland schools. A total of 352 school leavers (43.1% male, mean age=17.14years) completed a questionnaire at Whitsunday Schoolies, Queensland, Australia on 23-24 November 2010. Nearly 49% of respondents had attended Choices. The survey included measures of alcohol use, illicit drug use and associated problems during Schoolies and a month prior to Schoolies. Results. After controlling for gender and pre-Schoolies drinking, school leavers who attended Choices were significantly less likely to report illicit drug use (OR=0.51, P<0.05) and problem behaviours (OR=0.40, P<0.01) than those who did not attend Choices. There was, however, no intervention effect in risky drinking (i.e. drank on 5 or more days, typical amount five or more standard drink and binge drank on 3 or more days) at Schoolies (OR=0.92, P=0.80). Discussion and Conclusions. Delivery of a youth-specific applied theatre prevention program employing a harm minimisation framework may be effective in reducing high-risk behaviours associated with alcohol consumption at celebratory events, even if young people expect to engage in excessive alcohol consumption. [Quek L-H, White A, Low C, Brown J, Dalton N, Dow D, Connor JP. Good choices, great future: An applied theatre prevention program to reduce alcohol-related risky behaviours during Schoolies. Drug Alcohol Rev 2012;31:897–902]

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

乙醛脱氢酶2( ALDH2) 基因研究进展及其与饮酒行为的关系

:亚洲人群中普遍存在突变型的乙醛脱氢酶2 ( ALDH2 3 2) 。此酶突变后活性缺失,导致乙醛在肝脏内大量 累积使突变携带者在喝酒后会有脸红等不适反应,因此这可能影响他们的饮酒行为。由于ALDH2 3 2 等位基因 与饮酒行为相关,它也可能与酒精引起的肝脏损伤及某些癌症密切相关,而且,它在不同的亚洲人群中有不同的频 率分布。近年来对ALDH2 3 2 等位基因的序列结构、表达及其重要功能等有了更深入的了解,对ALDH2 的多态 性在研究方法、研究群体分布范围等都有很大进展。同时还讨论了不同地理分布、不同年龄结构、性别差异条件 下,中国人群中ALDH2 基因型频率与饮酒行为的关系。

Detection of usual and atypical aldehyde dehydrogenase alleles by mismatch amplification mutation assay

The genotypes of liver mitochondrial high-affinity aldehyde dehydrogenase-2 (ALDH2) are strongly associated with the drinking behavior and the alcohol liver diseases, since the individuals with atypical ALDH(2)(2) allele have higher levels of acetaldehyde in their plasma. The atypical ALDH(2)(2) allele has a nucleotide base transition (G-->A) in its exon 12. Based on this point mutation, we developed a rapid, reliable and inexpensive method, mismatch amplification mutation assay (MAMA), for the determination of human ALDH2 usual and atypical alleles. Two pairs of primers were designed for the amplification of the usual ALDH(2)(1) allele and the atypical ALDH(2)(2) allele, respectively. If the sample for the detection was heterozygous, it could be amplified by both of the primers. The product of polymerase chain reaction (PCR) of ALDH2 exon 12 could be easily screened by electrophoresis on a 2% agarose gel. The results of the MAMA method were further confirmed by sequencing. In the total of fifty samples from unrelated healthy Chinese Han people from Wuhan, China, the frequency of atypical ALDH(2)(2) allele was found to be 12%.

L-Type calcium channels mediate water intake induced by angiotensin injection into median preoptic nucleus

Calcium ions are widely accepted as critically important in responses of neurons to a stimulus. We have show previously the central involvement of angiotensin II (ANGII) in water intake. This study determined whether voltage-dependent calcium channels are involved in ANGII-induced behavioral drinking implicating nitrergic mechanism. The antidipsogenic actions of L-type calcium channel antagonists nifedipine, on ANGII-induced drinking behavior were studied when it is injected into the median preoptic nucleus (MnPO). The influence of nitric oxide (NO) on nifedipine antidipsogenic action was also studied by utilizing the N-W-nitro-L-arginine methyl ester (L-NAME) a constitutive nitric oxide synthase inhibitor constitutive (cNOSI) and 7-nitroindazol (7-NIT) a specific neuronal nitric oxide synthase inhibitor (nNOSI) and L-arginine a NO donor. Rats 200-250 g, with cannulae implanted into MnPO, pre-treated into MnPO with either nifedipine, followed by ANGII, drank significantly less water than controls during the first 15 min after injection. However, L-NAME potentiated the dipsogenic effect of ANGII that is blocked by prior injection of nifedipine and L-arginine. 7-NIT injected prior to ANGII into MnPO also potentiated the dipsogenic effect of ANGII but with a less intensity than L-NAME that it is also blocked by prior injection of nifedipine. The results described in this paper provide evidence that calcium channels play important roles in the ANGII-induced behavioral water intake. The structures containing NO in the brain such as MnPO include both endothelial cells and neurons might be responsible for the influence of nifedipine on dipsogenic effect of ANGII. These data shows the correlation between L-type calcium channel and a free radical gas NO produced endogenously from amino acids L-arginine by endothelial and neuronal NO synthase in the control of ANGII-dipsogenic effect. This suggests that an L-type calcium channel participates in both short- and longer-term neuronal actions of ANGII by nitrergic way. (c) 2006 Elsevier B.V. All rights reserved.

Central nitrergic system regulation of neuroendocrine secretion, fluid intake and blood pressure induced by angiotensin-II

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Consumo de álcool entre estudantes do ensino médio do município de Passos - MG

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The lateral preoptic area plays a dual role in the regulation of thirst in the rat

Electrolyte lesion and ibotenic acid lesion of the lateral preoptic area (LPO) of the rat were used to study the participation of this area in drinking behavior. Drinking was induced by cellular dehydration, hypovolemia, hypotension, and water deprivation. The animals with electrolytic lesion of the LPO showed a significant reduction in water intake in response to cellular dehydration, hypotension, and deprivation. The animals with ibotenic acid lesion of the LPO increased the water consumption produced by subcutaneous (SC) injection of hypertonic saline. The amount of water intake after SC injection of polyethyleneglycol (PEG) or isoprenaline was similar in control and ibotenic acid-lesioned animals. The rats with ibotenic acid lesion of the LPO drank significantly more water than control animals. Fibers of passage may also influence the drinking response, and the LPO may have osmosensitive receptors that facilitate water intake in connection with other areas of the central nervous system (CNS) that are implicated in drinking behavior.