Neurochemical Studies of Genetic Differences in Alcohol Action

Allan, Andrea M.; Harris, R. Adron

doi:10.1007/978-1-4899-2067-6_3

Cited by 29 publications

(9 citation statements)

References 145 publications

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“…Mice were successfully selectively bred for long (Long Sleep, or LS) or short (Short Sleep, or SS) duration of LRR to produce two selected lines that differ markedly (McClearn and Kakihana, 1981), proving the genetic contribution to this response. Many subsequent studies have explored the neurobiology of this trait (for reviews see Allan and Harris, 1991;Draski and Deitrich, 1996;Phillips and Crabbe, 1991). Recent studies have used LS and SS mice, and specific strains derived from them, to identify the genomic location of several genes influencing this response Markel et al, 1997;Owens et al, 2002).…”

Section: Introductionmentioning

confidence: 98%

Effects of Genetic and Procedural Variation on Measurement of Alcohol Sensitivity in Mouse Inbred Strains

et al. 2006

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Mice from eight inbred strains were studied for their acute sensitivity to ethanol as indexed by the degree of hypothermia (HT), indexed as the reduction from pre-injection baseline of their body temperature. Two weeks later, mice were tested for their loss of righting reflex (LRR) after a higher dose of ethanol. The LRR was tested using the "classical" method of watching for recovery in animals placed on their backs in a V-shaped trough and recording duration of LRR. In a separate test, naive animals of the same strains were tested for HT repeatedly to assess the development of rapid (RTOL) and chronic tolerance (CTOL). We have recently developed a new method for testing LRR that leads to a substantial increase in the sensitivity of the test. Strains also have been found to differ in the new LRR test, as well as in the development of acute functional tolerance (AFT) to this response. In addition, our laboratory has periodically published strain difference data on the older versions of the HT and LRR responses. The earlier tests used some of the exact substrains tested currently, while for some strains, different substrains (usually, Nih versus Jax) were tested. We examined correlations of strain means to see whether patterns of strain differences were stable across time and across different test variants assessing the same behavioral construct. HT strain sensitivity scores were generally highly correlated across a 10-23 years period and test variants. The CTOL to HT was well-correlated across studies, and was also genetically similar to RTOL. The AFT, however, was related to neither RTOL nor CTOL, although this may be because different phenotypic end points were compared. The LRR data, which included a variant of the classical test, were not as stable. Measures of LRR onset were reasonably well correlated, as were those taken at recovery (e.g., duration). However, the two types of measures of LRR sensitivity to ethanol appear to be tapping traits that differ genetically. Also, the pattern of genetic correlation between HT and LRR initially reported in 1983 was not seen in current and contemporaneous studies. In certain instances, substrain seems to matter little, while in others, substrains differed a great deal. These data are generally encouraging about the stability of genetic differences.

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Section: Introductionmentioning

confidence: 98%

Effects of Genetic and Procedural Variation on Measurement of Alcohol Sensitivity in Mouse Inbred Strains

et al. 2006

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“…During the past few years, attention has shifted from nonspecific membrane perturbation to actions on specific brain proteins. Initial biochemical and genetic studies suggested the y-aminobutyrate type A (GABAA) receptor as a site for alcohol actions (1)(2)(3)(4). Subsequent molecular cloning identified the GABAA receptor as a member of the ligand-gated superfamily of ion channels, leading to experiments showing that all members of this superfamily are sensitive to ethanol (5,6).…”

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confidence: 99%

Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors.

Harris

McQuilkin

Paylor

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

230

156

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Calcium/phospholipid-dependent protein kinase (protein kinase C, PKC) has been suggested to play a role in the sensitivity of y-aminobutyrate type A (GABAA) receptors to ethanol. We tested a line of null mutant mice that lacks the 'y isoform of PKC (PKCy) to determine the role of this brain-specific isoenzyme in ethanol sensitivity. We found that the mutation reduced the amount of PKCy immunoreactivity in cerebellum to undetectable levels without altering the levels of the a, 8j3, or Pu isoforms of PKC. The

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“…What have we learned from inbred strain studies of alcohol-related phenotypes since 1959? When the inbred strain literature on behavioural responses (Phillips & Crabbe 1991) and neurochemical strain differences (Allan & Harris 1991) were first comprehensively reviewed in 1991, only a handful of studies were published and these were nearly all limited to comparisons of the C57BL /6J and DBA /2J strains, previously identified as outliers for alcohol drinking and for the severity of alcohol withdrawal ( Kakihana 1979). However, the development of recombinant inbred (RI) strains (Bailey 1971) extended the use of inbred strains to a new purpose.…”

Section: Inbred Strainsmentioning

confidence: 99%

Neurogenetic studies of alcohol addiction

Crabbe

2008

Phil. Trans. R. Soc. B

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Neurogenetic studies of alcohol dependence have relied substantially on genetic animal models, particularly rodents. Studies of inbred strains, selectively bred lines and mutants bearing genes whose function has been targeted for over or under expression are reviewed. Studies focused on gene expression changes are the most recent contributors to this literature, and some genetic effects may work through epigenetic mechanisms. In a few instances, interesting parallels have been revealed between genetic risk in humans and studies in non-human animal models. Future approaches are likely to be increasingly complex.

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Neurochemical Studies of Genetic Differences in Alcohol Action

Cited by 29 publications

References 145 publications

Effects of Genetic and Procedural Variation on Measurement of Alcohol Sensitivity in Mouse Inbred Strains

Effects of Genetic and Procedural Variation on Measurement of Alcohol Sensitivity in Mouse Inbred Strains

Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors.

Neurogenetic studies of alcohol addiction

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