Genetic studies of alcohol dependence in the context of the addiction cycle
Alcohol dependence is heritable. Two factor contribute to alcohol dependence - environmental conditions, and genes. It is estimated that genes contribute to about 50-60% of the phenotype.It is hard to nail down the exact genes because everything is heterogenous. Researchers study twin studies and adoption data to define the genetic components of alcohol dependence. Both twin and adoption studies show high correlation between family members and the participants susception to alcohol dependency. Research then ran an GWAS (genome wide association study) and found multiple genetic variants that contribute to alcoholism.
The Evolution of Drosophila melanogaster as a Model for Alcohol Research
In this paper, researchers investigate the relationship between ethanol and Drosophila in an ecological and evolutionary perspective. Fruit flies have many adaptations due to a prevalence of ethanol in their environment. Typically fruit flies are found near ripe food which can hold up to 5% ethanol. Flies metabolize ethanol and use it as an energy source. Fruit flies also contain a smaller version of Alcohol Dehydrogenase (ADH) which differs slightly from the longer vertebrate version of the protein, indicating that fruit flies had an earlier ecological change to ethanol in ripe fruit. ADH is also necessary for survival on ethanol foods. Researchers found that having ethanol as the only source of calories induced a longer survival rate indicating that ethanol is a strong source of calories for Drosophila. Behavioral studies of Drosophila have shown that fruit flies with a longer and stronger exposure to ethanol ...
Ethanol Sensitivity and Tolerance in Long-Term Memory Mutants of Drosophila melanogaster - Berger - 2008 - Alcoholism: Clinical and Experimental Research - Wiley Online Library
Mutants of the learning and/or memory pathways have differential responses to ethanol tolerance. Some mutants increased amnesia/learning loss, while others had an opposite effect to ethanol tolerance. Researchers tested a collection of 60 long-term memory mutants for 52 loci where these mutants limit learning so normal function of each mutation are thought to play into the long-term memory pathway. Researchers then ran an ethanol assay and quantified the ethanol tolerance of each mutant. The data suggests that these pathways overlap and suggest specific genes for each pathway.
Dopamine modulates acute responses to cocaine, nicotine and ethanol in Drosophila
In this paper researchers study the role of dopamine in different drug exposures. To test how flies responded to cocaine and nicotine they tested how quickly they could climb up a glass tube. With the effects of the drug, flies would remain at the bottom of the tube. Cocaine recovery time was fifteen minutes for moderate doses and nicotine was five minutes for moderate doses. To test the effects of Dopamine, researchers used Dopamine depleted flies by feeding them a competitive antagonist to tyrosine hydroxylase which in necessary for dopamine synthesis. A complete lack of Dopamine results in lethality, so flies tested only have significantly reduced dopamine in their systems. When these flies were tested with cocaine or nicotine they shows a 35% reduction in ability to geotax (climb). These factors are contributed to dopamine reductions, due to a normalized response when the dopamine reduction was rev ...
In this paper the author tested the effect of ethanol consumption on Drosphila's courtship patterns and fecundity rate. Virgin males are separated into two groups; one getting food with water and one made with ethanol. Food consumption was highly regulated for 4 days. After four days males were combined with virgin females. They observed a significantly shorter courtship period, but a significant higher fecundity rates for flies with ethanol exposures. Flies also prefered ethanol food significantly to water food.
Repeated stress exposure results in a survival–reproduction trade-off in Drosophila melanogaster | Proceedings of the Royal Society of London B: Biological Sciences
Researchers took 35 isogenic female lines from London, Ontario, Canada where the multiple cold cycles occur. They grew flies up from these different lines and sorted them via CO2 anesthetics, with 15 Virgin females per vial and 30 virgin males per vial. Both male and female vials were stored at 22 degrees Celsius. Females, after waiting 3 days to eliminate possibility of CO2 effects the flies, the flies where placed into one of four groups in order to control for varying conditions. One group contained flies only exposed to 22 degrees C. One was exposed to -.5 degrees C for 10 hrs. Another was a multiple cold exposure, where flies were either exposed to 2, 3, 4, or 5 two hour periods of -.5 degrees C, with 22 hrs in between exposure times and ending at 7 days old to account for age influences. The last group was a single ...
PLOS ONE: The Esg Gene Is Involved in Nicotine Sensitivity in Drosophila melanogaster
In this article authors attempted to identify genes that are involved in nicotine sensitivity. They tested white1118 (w1118) flies against different mutants by exposing each group of flies to nicotine that was dissolved in water and then aerosolized. The parameter focused on was Half Recovery Time (HRT). HRT is the time it takes for half of a group of flies to recover from volatilized nicotine. For w1118 flies the standard amount of nicotine given based on the HRT was 32 ng of nicotine over 30 minutes. The mutant lines L4 and L70 had a significantly different response to nicotine exposure. Both showed an increase in hypersensitivity. L4 is an escargot (esg) loss-of-function gene, where L70 seems to down regulate esg genes. To test that L4 actually creates a loss of function is esg genes, researchers mutated other known esg regulating genes and exposed them to the same nicotine tests with their ...
In this paper, scientists use drosophila melanogaster to study variation in alcohol-related phenotypes. Using the sequenced, inbred lines of Drosophila melanogaster Genetic Reference Panel (DGRP) coupled with extreme QTL mapping, a genome wide association analysis was performed on both resistant and sensitive DGRP lines. 247 candidate genes were identified to have an affect on DGRP or DGRP-derived populations. Many of these genes were tied to development and nervous system function. 58 of these genes were found to form a genetic network. Two thirds of the genes found have been implicated through previous studies. Authors conclude by stating that individual variation is highly polygenic and are partway determined by evolutionary pathways that are linked to neurodevelopmental genes.
Fruit Flies in Biomedical Research | Genetics
The authors in this paper discuss primarily the importance of Drosophila in science. They discuss how funding for Drosophila research has decreased dramatically and reminds readers of the benefits of using Drosophila as a model for biomedical research. Authors discuss specific advancements in genetic research, immunology, cancer research, neurobiology, etc. They explain what genes in drosophila are key to understanding their human homologs, specifically stating the x-chromosome screen and what scientists have learned from that. They found that more than 90% of genes found in this screening had a human homolog. Authors then argue that even when drosophila are used to test for genes that don't have a specific human homolog that they can still lead to pertinent information about human biology. They further argue that drosophila lead to the discoveries of human disease and how best to treat disease. In the conclusion they remind the reader t ...
Drosophila melanogaster as a model to study drug addiction | SpringerLink
The authors of this paper defend why using Drosophila Melanogaster as a model to study drug addiction. They discuss that this is species contains 75% human disease genes which makes them optimal for studying a disease related behavior. Drosophila melanogaster also have a high fecundity level, cost, size, and timescale. In other words they reproduce quickly and be fully mature within 10 days. They are relatively inexpensive and can be reared in bottle. Ethanol-related behaviors are a large focus on this paper. Ethanol tolerance had been studied most intensely in Drosophila, and is "pyschoactive drug that can produce both short-term impairment as well as long term addiction." Ethanol tolerance or addiction is a predisposition for Drosophila Melanogaster, which makes the study of this species ideal for addictive behaviors. "Female flies prefer to lay to lay their eggs in media containing up to 5% ethanol, and lar ...