The firewater myth and response to alcohol in Mission Indians

Garcia‐Andrade, Consuelo; Wall, Tamara L.; Ehlers, Cindy L.

doi:10.1176/ajp.154.7.983

Cited by 50 publications

(12 citation statements)

References 39 publications

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“…BxN mice exhibiting reduced alcohol preference consumed less than would be expected from a typical C57BL/6J mouse [1]. Therefore, although we did not take blood alcohol samples, it is not likely that BxN mice showing reduced alcohol preference achieved sustained pharmacologically relevant blood alcohol levels, suggesting high blood alcohol concentrations of are not necessary to induce plasticity on these brain regions.…”

Section: Discussionmentioning

confidence: 99%

“…Offspring were weaned into isosexual groups of each of the genotypes (BxF F1, BxN F1). We tested only female mice to facilitate comparison with previously collected data [1,5,6]. Mice were housed in standard cages with food and water provided ad libitum .…”

Section: Methodsmentioning

confidence: 99%

“…The ability to drink copious amounts of alcohol with little consequence to the individual is a primary onset symptom in many alcoholics, indicating that a low level of response to alcohol is a major vulnerability factor in the development of alcoholism [1,2]. Defining neurobiological factors contributing to alcohol moderation will aid our understanding of alcohol use and abuse, and is an effective strategy for the development of improved treatments for individuals diagnosed with alcohol use disorders.…”

Section: Introductionmentioning

confidence: 99%

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Chronic self-administration of alcohol results in elevated ΔFosB: comparison of hybrid mice with distinct drinking patterns

et al. 2012

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BackgroundThe inability to reduce or regulate alcohol intake is a hallmark symptom for alcohol use disorders. Research on novel behavioral and genetic models of experience-induced changes in drinking will further our knowledge on alcohol use disorders. Distinct alcohol self-administration behaviors were previously observed when comparing two F1 hybrid strains of mice: C57BL/6J x NZB/B1NJ (BxN) show reduced alcohol preference after experience with high concentrations of alcohol and periods of abstinence while C57BL/6J x FVB/NJ (BxF) show sustained alcohol preference. These phenotypes are interesting because these hybrids demonstrate the occurrence of genetic additivity (BxN) and overdominance (BxF) in ethanol intake in an experience dependent manner. Specifically, BxF exhibit sustained alcohol preference and BxN exhibit reduced alcohol preference after experience with high ethanol concentrations; however, experience with low ethanol concentrations produce sustained alcohol preference for both hybrids. In the present study, we tested the hypothesis that these phenotypes are represented by differential production of the inducible transcription factor, ΔFosB, in reward, aversion, and stress related brain regions.ResultsChanges in neuronal plasticity (as measured by ΔFosB levels) were experience dependent, as well as brain region and genotype specific, further supporting that neuronal circuitry underlies motivational aspects of ethanol consumption. BxN mice exhibiting reduced alcohol preference had lower ΔFosB levels in the Edinger-Westphal nucleus than mice exhibiting sustained alcohol preference, and increased ΔFosB levels in central medial amygdala as compared with control mice. BxN mice showing sustained alcohol preference exhibited higher ΔFosB levels in the ventral tegmental area, Edinger-Westphal nucleus, and amygdala (central and lateral divisions). Moreover, in BxN mice ΔFosB levels in the Edinger-Westphal nucleus and ventral tegmental regions significantly positively correlated with ethanol preference and intake. Additionally, hierarchical clustering analysis revealed that many ethanol-naïve mice with overall low ΔFosB levels are in a cluster, whereas many mice displaying sustained alcohol preference with overall high ΔFosB levels are in a cluster together.ConclusionsBy comparing and contrasting two alcohol phenotypes, this study demonstrates that the reward- and stress-related circuits (including the Edinger-Westphal nucleus, ventral tegmental area, amygdala) undergo significant plasticity that manifests as reduced alcohol preference.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic self-administration of alcohol results in elevated ΔFosB: comparison of hybrid mice with distinct drinking patterns

et al. 2012

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“…The present report is part of a larger study exploring risk factors for alcoholism in a Native American community (Ehlers and Wilhelmsen, 2005; Ehlers et al, 1998, 1999, 2001a,2001b, 2004a, 2004b; Garcia-Andrade et al, 1996, 1997; Gilder et al, 2002; 2004; Wall et al, 1996, 2000, 2003). In previous studies, we have demonstrated the utility of examining evidence of linkage and association using the alcohol dependence diagnosis as well as a severe use and a withdrawal phenotype, with the latter phenotypes selected to identify a more severe form of alcohol dependence given the high prevalence rate of alcohol dependence in this sample.…”

Section: Introductionmentioning

confidence: 98%

Association of Alcohol Dehydrogenase Genes with Alcohol-Related Phenotypes in a Native American Community Sample

Gizer

Edenberg

Gilder

et al. 2011

Alcoholism: Clinical and Experimental Research

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Background Previous linkage studies, including a study of the Native American population described in the present report, have provided evidence for linkage of alcohol dependence and related traits to chromosome 4q near a cluster of alcohol dehydrogenase (ADH) genes, which encode enzymes of alcohol metabolism. Methods The present study tested for associations between alcohol dependence and related traits and 22 single nucleotide polymorphisms (SNPs) spanning the seven ADH genes. Participants included 586 adult men and women recruited from eight contiguous Native American reservations. A structured interview was used to assess DSM-III-R alcohol dependence criteria as well as a set of severe alcohol misuse symptoms and alcohol withdrawal symptoms. Results No evidence for association with the alcohol dependence diagnosis was observed, but a SNP in exon 9 of ADH1B (rs2066702; ADH1B*3) and a SNP at the 5' end of ADH4 (rs3762894) showed significant evidence of association with the presence of withdrawal symptoms (p=0.0018 and 0.0012, respectively). Further, a haplotype analysis of these two SNPs suggested haplotypes containing either of the minor alleles were protective against alcohol withdrawal relative to the ancestral haplotype (p=0.000006). Conclusions These results suggest that variants in the ADH1B and ADH4 genes may be protective against the development of some symptoms associated with alcohol dependence.

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“…Empirical studies of alcohol drinking in the laboratory, in Native Americans, provide little support for such theories (Garcia-Andrade et al, 1997). However, investigations of potential differences in alcohol metabolism are a logical avenue of research that may be capable of explaining some of the variance in ethnic differences in response to alcohol and in the development of alcohol dependence.…”

Section: Introductionmentioning

confidence: 99%

Association and ancestry analysis of sequence variants in ADH and ALDH using alcohol‐related phenotypes in a Native American community sample

Peng

Gizer

Libiger

et al. 2014

American J of Med Genetics Pt B

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Higher rates of alcohol use and other drug-dependence have been observed in some Native American populations relative to other ethnic groups in the U.S. Previous studies have shown that alcohol dehydrogenase (ADH) genes and aldehyde dehydrogenase (ALDH) genes may affect the risk of development of alcohol dependence, and that polymorphisms within these genes may differentially affect risk for the disorder depending on the ethnic group evaluated. We evaluated variations in the ADH and ALDH genes in a large study investigating risk factors for substance use in a Native American population. We assessed ancestry admixture and tested for associations between alcohol-related phenotypes in the genomic regions around the ADH1-7 and ALDH2 and ALDH1A1 genes. Seventy-two (72) ADH variants showed significant evidence of association with a severity level of alcohol drinking-related dependence symptoms phenotype. These significant variants spanned across the entire 7 ADH gene cluster regions. Two significant associations, one in ADH and one in ALDH2, were observed with alcohol dependence diagnosis. Seventeen (17) variants showed significant association with the largest number of alcohol drinks ingested during any 24-hour period. Variants in or near ADH7 were significantly negatively associated with alcohol-related phenotypes, suggesting a potential protective effect of this gene. In addition, our results suggested that a higher degree of Native American ancestry is associated with higher frequencies of potential risk variants and lower frequencies of potential protective variants for alcohol dependence phenotypes.

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The firewater myth and response to alcohol in Mission Indians

Cited by 50 publications

References 39 publications

Chronic self-administration of alcohol results in elevated ΔFosB: comparison of hybrid mice with distinct drinking patterns

Chronic self-administration of alcohol results in elevated ΔFosB: comparison of hybrid mice with distinct drinking patterns

Association of Alcohol Dehydrogenase Genes with Alcohol-Related Phenotypes in a Native American Community Sample

Association and ancestry analysis of sequence variants in ADH and ALDH using alcohol‐related phenotypes in a Native American community sample

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