Common Quantitative Trait Loci for Alcohol‐Related Behaviors and CNS Neurotensin Measures: Voluntary Ethanol Consumption

Gehle, Vaughn M.; Erwin, V. Gene

doi:10.1111/j.1530-0277.1998.tb03666.x

Cited by 24 publications

(26 citation statements)

References 59 publications

(5 reference statements)

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“…Finally, it is possible that tolerance and drinking are genetically related in rats but not in mice. Indeed, previous studies in mice have shown little genetic co-variation between alcohol preference and measures of tolerance (Gehle and Erwin 1998, but see Erwin et al 1980). Further studies would have to be done to assess this potential species difference.…”

Section: Discussionmentioning

confidence: 96%

Ethanol locomotor sensitization, but not tolerance correlates with selection for alcohol preference in high- and low-alcohol preferring mice

Grahame¹,

Rodd-Henricks²,

et al. 2000

Psychopharmacology

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Section: Discussionmentioning

confidence: 96%

Ethanol locomotor sensitization, but not tolerance correlates with selection for alcohol preference in high- and low-alcohol preferring mice

Grahame¹,

Rodd-Henricks²,

et al. 2000

Psychopharmacology

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“…Several overlapping regions on chromosome 15 were identified as QTL acting on ethanol consumption in previous studies (Gehle & Erwin, 1998 ;Phillips et al 1998 ;Tarantino et al 1998 ;Vadasz et al 2000a, b).…”

Section: Genetics Of Ethanol Responses 165mentioning

confidence: 88%

“…Previously trait-related QTL on the chromosome : 1 Htas1, 83.6 cM (Crabbe, 1994) ; 2 Ap7q, 25 cM (MGI) ; 3 Htas6, 60 cM (Crabbe, 1994) ; 4 Htas5, 63 cM (Crabbe, 1994) (Gill et al 1996) ; 14 EtOH preference QTL, 4 cM (Gill et al 1998) ; 15 Drb7, 45 cM, Lore5, 46 cM (MGI), EtOH consumption QTL (Gehle & Erwin, 1998 ;Phillips et al 1998 ;Tarantino et al 1998 ;Vadasz et al 2000 a, b).…”

Section: Chronic Ethanol Consumption and Withdrawalmentioning

confidence: 97%

Quantitative trait loci contributing to physiological and behavioural ethanol responses after acute and chronic treatment

Drews¹,

Rácz²,

Lacava³

et al. 2009

Int. J. Neuropsychopharm.

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The aim of the present study was the identification of gene loci that contribute to the development and manifestation of behaviours related to acute and chronic alcohol exposure, as well as to alcohol withdrawal. For this purpose, we performed a serial behavioural phenotyping of 534 animals from the second filial (F2) generation of a C57BL/6J and C3H/HeJ mice intercross in paradigms with relevance to alcohol dependence. First, ethanol-induced hypothermia was determined in ethanol-naive animals. The mice then received an ethanol solution for several weeks as their only fluid source. Ethanol tolerance, locomotor activity and anxiety-related behaviours were evaluated. The ethanol was next withdrawn and the withdrawal severity was assessed. The ethanol-experienced animals were finally analysed in a two-bottle choice paradigm to determine ethanol preference and stress-induced changes in ethanol preference. The genotypes of these mice were subsequently assessed by microsatellite marker mapping. We genotyped 264 markers with an average marker distance of 5.56 cM, which represents a high-density whole genome coverage. Quantitative trait loci (QTL) were subsequently identified using univariate analysis performed with the R/qtl tool, which is an extensible, interactive environment for mapping QTL in experimental crosses. We found QTL that have already been published, thus validating the serial phenotyping protocol, and identified several novel loci. Our analysis demonstrates that the various responses to ethanol are regulated by independent groups of genes.

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“…The activation of dopamine neurotransmission in the nucleus accumbens is thought to be involved in the motivational and reward properties of alcohol and other abused drugs [Koob and Le Moal, 1997;Tanda et al, 1997]. Recent quantitative trait loci studies of mouse models of alcoholism [Gehle and Erwin, 1998;Phillips et al, 1994;Tarantino et al, 1998] found linkage between the D 2 dopamine receptor (DRD2) gene and alcohol preference, suggesting a genetic basis for this behavior. Moreover, studies of genetically manipulated animals further support a role for the dopaminergic system in alcohol and other drugs of abuse.…”

mentioning

confidence: 99%

Haplotypes at theDRD2 locus and severe alcoholism

et al. 2000

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Association studies of the minor TaqI A allele of the D(2) dopamine receptor (DRD2) gene with alcoholism have produced conflicting findings. Failure to assess alcoholics for severity of their disorder and to screen controls for substance use have been proposed as causes for the discrepant results. In the present study, five diallelic sites spanning the DRD2 gene were determined in combined Caucasian (non-Hispanic) studies of more severe alcoholics (n = 92) and controls screened for substance use (n = 85). The frequency of the minor alleles at the 3'-untranslated site (TaqI A) and two intronic sites (TaqI B and intron 6) of the DRD2 gene were each strongly associated with alcoholism. Moreover, the alcoholics compared with the controls at these three sites had a significantly higher frequency of the minor/major allele heterozygote haplotype combination (A1/A2 B1/B2 T/G) than the major allele homozygote haplotype combination (A2/A2 B2/B2 G/G). However, exon 7 and promoter alleles were not associated with alcoholism. In neither the alcoholics nor in the controls were there departures from Hardy-Weinberg equilibrium at any of the five sites examined. The most significant diallelic composite genotypic disequilibria were found when comparisons were made between TaqI A and TaqI B, TaqI A and intron 6, and TaqI B and intron 6 sites. Weaker but still significant disequilibria were observed when TaqI A and exon 7, TaqI B and exon 7, intron 6 and exon 7, and promoter and exon 7 sites were compared. However, no significant disequilibria were noted when TaqI A and promoter, TaqI B and promoter, and intron 6 and promoter sites were compared. In sum, the study found significant evidence for association of the minor alleles in the untranslated sites of the DRD2 gene and their haplotypes with the more severe alcoholic phenotype.

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Common Quantitative Trait Loci for Alcohol‐Related Behaviors and CNS Neurotensin Measures: Voluntary Ethanol Consumption

Cited by 24 publications

References 59 publications

Ethanol locomotor sensitization, but not tolerance correlates with selection for alcohol preference in high- and low-alcohol preferring mice

Ethanol locomotor sensitization, but not tolerance correlates with selection for alcohol preference in high- and low-alcohol preferring mice

Quantitative trait loci contributing to physiological and behavioural ethanol responses after acute and chronic treatment

Haplotypes at theDRD2 locus and severe alcoholism

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