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Full-Text Articles in Medicine and Health Sciences
An Analysis Of Fatty Acid Metabolism’S Role In The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans, Richard Raabe
An Analysis Of Fatty Acid Metabolism’S Role In The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans, Richard Raabe
Theses and Dissertations
An individual’s naïve level of response (LR) to ethanol is predictive of their lifetime likelihood to abuse alcohol. LR is heavily genetically influenced, suggesting that the genes responsible for LR may also be central to the development of abuse disorders. Our laboratory uses the model organism C. elegans to investigate the genetic influences on responses to acute ethanol exposure. We recently found that changes in TAG levels can alter LR. From this result we investigated the role of long-chain polyunsaturated fatty acids (LC-PUFAs) as well enzymes involved in lipid modifications of proteins. We found that LC-PUFAs are necessary for acute …
Behavioral And Genomic Characterization Of Scheduled Ethanol Deprivation, Jonathan Warner
Behavioral And Genomic Characterization Of Scheduled Ethanol Deprivation, Jonathan Warner
Theses and Dissertations
Alcoholism is a persistent substance abuse disorder that is associated with negative health, social, and economic outcomes. Treatment strategies for alcohol use disorders are limited, and only three drugs have been approved by the FDA for treatment. Although behavioral therapy and drug combination strategies improve abstinence outcomes, the majority of those in treatment will not achieve long-term abstinence. Therefore, better treatment strategies are needed. While much progress has been made toward understanding the neurobiology of alcoholism, this knowledge has not been effectively translated into treatment strategies. Animal models of alcohol drinking have been crucial to this research effort, but until …
Identification And Characterization Of Ethanol Responsive Genes In Acute Ethanol Behaviors In Caenorhabditis Elegans, Joseph Alaimo
Identification And Characterization Of Ethanol Responsive Genes In Acute Ethanol Behaviors In Caenorhabditis Elegans, Joseph Alaimo
Theses and Dissertations
Alcohol abuse and dependence are complex disorders that are influenced by many genetic and environmental factors. Acute behavioral responses to ethanol have predictive value for determining an individual’s long-term susceptibility to alcohol abuse and dependence. These behavioral responses are strongly influenced by genetics. Here, we have explored the role of genetic influences on acute behavioral responses to ethanol using the nematode worm, Caenorhabditis elegans. First, we explored the role of ethanol metabolism in acute behavior responses to ethanol. Natural variation in human ethanol metabolism machinery is one of the most reported and reproducible associations found to alter drinking behavior. Ethanol …
Ethanol Regulation Of Glucocorticoid Responsive Genes, Blair Costin
Ethanol Regulation Of Glucocorticoid Responsive Genes, Blair Costin
Theses and Dissertations
Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. Acute ethanol activates the hypothalamic pituitary adrenal (HPA) axis causing the release of adrenal glucocorticoid hormones, but following chronic ethanol the HPA axis is dysregulated in both humans and rodents. Thus, there is growing evidence that glucocorticoids might also modulate behavioral and molecular responses to ethanol. Previous microarray studies in the Miles’ laboratory have shown that the well-known glucocorticoid responsive gene, Serum and Glucocorticoid-regulated Kinase 1, Sgk1, is prominently up regulated by acute ethanol (2 g/kg) in the prefrontal cortex (PFC) of …
Identifying Modulators Of The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans., Ka-Po Leung
Identifying Modulators Of The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans., Ka-Po Leung
Theses and Dissertations
Alcohol abuse is a problem in our society. There are few treatments available, in part due to the unclear molecular mechanisms of ethanol’s effects. Human studies indicate that there is a genetic component influencing disease susceptibility, and that an individual’s initial response to alcohol can predict their development of addiction. We have taken a forward genetics approach to study one component of initial response, acute functional tolerance (AFT), in Caenorhabditis elegans. We identified bet11, a mutation that causes animals to be defective in the development of AFT. Genetic analysis suggested that the gene that bet11 disrupts participates in a synthetic …
Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme
Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme
Theses and Dissertations
A majority of Americans regularly consume alcohol, but the risk factors leading to excessive drinking and alcohol abuse are unevenly distributed throughout the population. Genetic differences can account for only 40-60% of this variability. While variations in ethanol preference drinking in rodent models have been reported, the neurobiological factors underlying these behaviors are still not completely understood. Thus, these studies were designed to determine behavioral and molecular factors associated with the initiation of ethanol drinking preference in an inbred mouse model. We harnessed the power of inter-individual variation of ethanol drinking within an inbred mouse strain to essentially eliminate genetic …