Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster

Koyyada, Rajeswari; Latchooman, Nilesh; Jonaitis, Julius; Ayoub, Samir S.; Corcoran, Olivia; Casalotti, Stefano O.

doi:10.3389/fphys.2018.00175

Cited by 10 publications

(8 citation statements)

References 30 publications

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“…Interspecies transcriptomic and proteomic analyses combined with behavioral mutant analyses will help to narrow the list of crucial regulators of AUDs. In the future, Drosophila and C. elegans can be used as screening platforms to test the efficacy of pharmacological compounds to disrupt alcohol‐related behaviors (Koyyada et al., ; Ranson et al., ; Scott et al., ,b). Finally, the use of Drosophila and C. elegans as genetic model organisms can also be extended to study other drugs of abuse, such as nicotine or cocaine (reviewed by Dupuis et al., ; Engleman et al., ; Haydon et al., ; Kaun et al., ; Kudelska et al., ; Lowenstein and Velazquez‐Ulloa, ; Matta et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…When flies are nonvoluntarily exposed to EtOH, they develop EtOH consumption preferences that are long‐lasting and independent of the EtOH's caloric value (Peru et al., ). The preference to consume EtOH‐enriched food can be reduced by feeding with naltrexone (Koyyada et al., ). In the Drosophila brain, cAMP signaling regulates EtOH consumption preference in the mushroom bodies, a brain structure required for appetitive olfactory learning and memory, using sugar as reward (Xu et al., ).…”

Section: Decision Making Reward and Learning: Dissecting Relationshmentioning

confidence: 99%

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Unraveling the Mechanisms of Behaviors Associated With AUDs Using Flies and Worms

Scholz

2019

Alcoholism Clin & Exp Res

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Alcohol use disorders (AUDs) are very common worldwide and negatively affect both individuals and societies. To understand how normal behavior turns into uncontrollable use of alcohol, several approaches have been utilized in the last decades. However, we still do not completely understand how AUDs evolve or how they are maintained in the brains of affected individuals. In addition, efficient and effective treatment is still in need of development. This review focuses on alternative approaches developed over the last 20 years using Drosophila melanogaster (Drosophila) and Caenorhabditis elegans (C. elegans) as genetic model systems to determine the mechanisms underlying the action of ethanol (EtOH) and behaviors associated with AUDs. All the results and insights of studies over the last 20 years cannot be comprehensively summarized. Thus, a few prominent examples are provided highlighting the principles of the genes and mechanisms that have been uncovered and are involved in the action of EtOH at the cellular level. In addition, examples are provided of the genes and mechanisms that regulate behaviors relevant to acquiring and maintaining excessive alcohol intake, such as decision making, reward and withdrawal, and/or relapse regulation. How the insight gained from the results of Drosophila and C. elegans models can be translated to higher organisms, such as rodents and/or humans, is discussed, as well as whether these insights have any relevance or impact on our understanding of the mechanisms underlying AUDs in humans. Finally, future directions are presented that might facilitate the identification of drugs to treat AUDs.

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Section: Discussionmentioning

confidence: 99%

Section: Decision Making Reward and Learning: Dissecting Relationshmentioning

confidence: 99%

Unraveling the Mechanisms of Behaviors Associated With AUDs Using Flies and Worms

Scholz

2019

Alcoholism Clin & Exp Res

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“…In this work, Drosophila was confirmed to be a useful model for studying alcohol-induced behaviours as has been amply demonstrated in other studies (Kaun et al, 2012; Robinson et al, 2013). Previous Drosophila work had identified a number of GPCRs that are involved in the response to alcohol, including the dopamine/ecdysteroid receptor (Petruccelli et al, 2016), neuropeptide F receptor (Wen et al, 2005), putative opioid receptors (Koyyada et al, 2018) and GABA B receptor (Ranson et al, 2019). An earlier extensive review of mammalian studies of the effect of psychostimulants on G-protein expression (Kitanaka et al, 2008) highlighted that only limited work had been focused on ethanol-induced changes in any animal models, with only one study reporting a reduction in G-protein b1 in rat hippocampus (Saito et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

G-protein αq gene expression plays a role in alcohol tolerance in Drosophila melanogaster

Aleyakpo

Umukoro

Kavlie

et al. 2019

Brain and Neuroscience Advances

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Ethanol is a psychoactive substance causing both short- and long-term behavioural changes in humans and animal models. We have used the fruit fly Drosophila melanogaster to investigate the effect of ethanol exposure on the expression of the Gαq protein subunit. Repetitive exposure to ethanol causes a reduction in sensitivity (tolerance) to ethanol, which we have measured as the time for 50% of a set of flies to become sedated after exposure to ethanol (ST50). We demonstrate that the same treatment that induces an increase in ST50 over consecutive days (tolerance) also causes a decrease in Gαq protein subunit expression at both the messenger RNA and protein level. To identify whether there may be a causal relationship between these two outcomes, we have developed strains of flies in which Gαq messenger RNA expression is suppressed in a time- and tissue-specific manner. In these flies, the sensitivity to ethanol and the development of tolerance are altered. This work further supports the value of Drosophila as a model to dissect the molecular mechanisms of the behavioural response to alcohol and identifies G proteins as potentially important regulatory targets for alcohol use disorders.

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“…Tests of similar learning and memory genes revealed additional notable alcohol phenotypes caused by manipulations of rutabaga (rut) [11,142,197,198], encoding fly adenylyl cyclase, and dnc [193,199,200]. Separate from these pathways and studies, other studies have suggested alcohol-related roles of other genes in the network, including the cAMP-dependent protein kinase A (PKA) [114,197,201], protein kinase C (PKC) [79,[202][203][204], CREB [205][206][207], and CREB binding protein (CBP) [117,208], consistently suggesting a causal role of cAMP signaling pathways in alcohol abuse. The K + channel KCNQ is another example of the one-gene-at-a-time approach and the phenomenon of fly and human studies autonomously arriving at corroborating conclusions.…”

Section: Behavioral Screens In Drosophilamentioning

confidence: 99%

Flying Together: Drosophila as a Tool to Understand the Genetics of Human Alcoholism

Lathen

Merrill

Rothenfluh

2020

IJMS

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Alcohol use disorder (AUD) exacts an immense toll on individuals, families, and society. Genetic factors determine up to 60% of an individual’s risk of developing problematic alcohol habits. Effective AUD prevention and treatment requires knowledge of the genes that predispose people to alcoholism, play a role in alcohol responses, and/or contribute to the development of addiction. As a highly tractable and translatable genetic and behavioral model organism, Drosophila melanogaster has proven valuable to uncover important genes and mechanistic pathways that have obvious orthologs in humans and that help explain the complexities of addiction. Vinegar flies exhibit remarkably strong face and mechanistic validity as a model for AUDs, permitting many advancements in the quest to understand human genetic involvement in this disease. These advancements occur via approaches that essentially fall into one of two categories: (1) discovering candidate genes via human genome-wide association studies (GWAS), transcriptomics on post-mortem tissue from AUD patients, or relevant physiological connections, then using reverse genetics in flies to validate candidate genes’ roles and investigate their molecular function in the context of alcohol. (2) Utilizing flies to discover candidate genes through unbiased screens, GWAS, quantitative trait locus analyses, transcriptomics, or single-gene studies, then validating their translational role in human genetic surveys. In this review, we highlight the utility of Drosophila as a model for alcoholism by surveying recent advances in our understanding of human AUDs that resulted from these various approaches. We summarize the genes that are conserved in alcohol-related function between humans and flies. We also provide insight into some advantages and limitations of these approaches. Overall, this review demonstrates how Drosophila have and can be used to answer important genetic questions about alcohol addiction.

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Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster

Cited by 10 publications

References 30 publications

Unraveling the Mechanisms of Behaviors Associated With AUDs Using Flies and Worms

Unraveling the Mechanisms of Behaviors Associated With AUDs Using Flies and Worms

G-protein αq gene expression plays a role in alcohol tolerance in Drosophila melanogaster

Flying Together: Drosophila as a Tool to Understand the Genetics of Human Alcoholism

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