Increased dopaminergic neurotransmission results in ethanol dependent sedative behaviors in Caenorhabditis elegans

Pandey, Pallavi; Singh, Anuradha; Kaur, Harjot; Ghosh-Roy, Anindya; Babu, Kavita

doi:10.1371/journal.pgen.1009346

Cited by 17 publications

(11 citation statements)

References 108 publications

(163 reference statements)

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“…We reasoned that among the genes that are regulated in response to ethanol exposure would be genes that had already been identified as having roles in acute ethanol response phenotypes. We compiled a list of 77 genes that had been confirmed by behavioral testing in our and others’ laboratories to affect ethanol response behaviors in C. elegans 2 , 11 , 31 , 38 – 49 and compared this list with the set of genes regulated at 480 min of ethanol exposure. We found that 21 of these genes were regulated at 480 min.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional analysis of the response of C. elegans to ethanol exposure

Sterken

Wijk

Quamme

et al. 2021

Sci Rep

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Ethanol-induced transcriptional changes underlie important physiological responses to ethanol that are likely to contribute to the addictive properties of the drug. We examined the transcriptional responses of Caenorhabditis elegans across a timecourse of ethanol exposure, between 30 min and 8 h, to determine what genes and genetic pathways are regulated in response to ethanol in this model. We found that short exposures to ethanol (up to 2 h) induced expression of metabolic enzymes involved in metabolizing ethanol and retinol, while longer exposure (8 h) had much more profound effects on the transcriptome. Several genes that are known to be involved in the physiological response to ethanol, including direct ethanol targets, were regulated at 8 h of exposure. This longer exposure to ethanol also resulted in the regulation of genes involved in cilia function, which is consistent with an important role for the effects of ethanol on cilia in the deleterious effects of chronic ethanol consumption in humans. Finally, we found that food deprivation for an 8-h period induced gene expression changes that were somewhat ameliorated by the presence of ethanol, supporting previous observations that worms can use ethanol as a calorie source.

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Section: Resultsmentioning

confidence: 99%

Transcriptional analysis of the response of C. elegans to ethanol exposure

Sterken

Wijk

Quamme

et al. 2021

Sci Rep

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“…Although several genes are implicated in addiction behavior, the mechanism by which binge episodes of alcohol consumption lead to addiction, however, remain largely elusive. Caenorhabditis elegans shows sedation and defects in locomotion in response to alcohol at a concentration similar to that seen in humans (Davies et al, 2003;Mitchell et al, 2007;Pandey et al, 2021). Therefore, C. elegans, with a simple nervous system and easy genetic manipulation, serves as a good model system for studying addiction behaviors and their underlying molecular mechanism.…”

Section: Addiction Behaviormentioning

confidence: 97%

“… Body bend and amplitude of a sinusoidal wave during locomotion in C. elegans. The image has been adapted from Pandey et al (2021) . …”

Section: Introductionmentioning

confidence: 99%

Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs

Bhat

Shahi

Surendran

et al. 2021

Front. Mol. Neurosci.

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One of the reasons that most multicellular animals survive and thrive is because of the adaptable and plastic nature of their nervous systems. For an organism to survive, it is essential for the animal to respond and adapt to environmental changes. This is achieved by sensing external cues and translating them into behaviors through changes in synaptic activity. The nervous system plays a crucial role in constantly evaluating environmental cues and allowing for behavioral plasticity in the organism. Multiple neurotransmitters and neuropeptides have been implicated as key players for integrating sensory information to produce the desired output. Because of its simple nervous system and well-established neuronal connectome, C. elegans acts as an excellent model to understand the mechanisms underlying behavioral plasticity. Here, we critically review how neuropeptides modulate a wide range of behaviors by allowing for changes in neuronal and synaptic signaling. This review will have a specific focus on feeding, mating, sleep, addiction, learning and locomotory behaviors in C. elegans. With a view to understand evolutionary relationships, we explore the functions and associated pathophysiology of C. elegans neuropeptides that are conserved across different phyla. Further, we discuss the mechanisms of neuropeptidergic signaling and how these signals are regulated in different behaviors. Finally, we attempt to provide insight into developing potential therapeutics for neuropeptide-related disorders.

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“…Increased activity of DAT and tyrosine hydroxylase has also been shown to correlate with D2 auto-receptor activation at saturating levels of ex vivo dopamine in Xenopus oocytes (Mayfield & Zahniser, 2001), and in vitro protein-protein interaction between DAT and the presynaptic D2 auto-receptor has been suggested to facilitate DAT recruitment to the cell surface (Lee et al, 2007). Interestingly, this recruitment tends to decrease in C. elegans mutants deleted in the D2 auto-receptor, upon ethanol exposure (Pandey et al, 2021). Optogenetic and voltammetric studies with rat hypothalamic dopamine neurons in culture suggest that auto-regulatory characteristics of these neurons are attributable to the re-uptake of synaptic dopamine by the dopamine transporter (Stagkourakis et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The dopamine membrane transporter plays an active modulatory role in synaptic dopamine homeostasis

Formisano

Rosikon

Singh

et al. 2021

J of Neuroscience Research

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Modulatory mechanisms of neurotransmitter release and clearance are highly controlled processes whose finely tuned regulation is critical for functioning of the nervous system. Dysregulation of the monoamine neurotransmitter dopamine can lead to several neuropathies. Synaptic modulation of dopamine is known to involve pre‐synaptic D2 auto‐receptors and acid sensing ion channels. In addition, the dopamine membrane transporter (DAT), which is responsible for clearance of dopamine from the synaptic cleft, is suspected to play an active role in modulating release of dopamine. Using functional imaging on the Caenorhabditis elegans model system, we show that DAT‐1 acts as a negative feedback modulator to neurotransmitter vesicle fusion. Results from our fluorescence recovery after photo‐bleaching (FRAP) based experiments were followed up with and reaffirmed using swimming‐induced paralysis behavioral assays. Utilizing our numerical FRAP data we have developed a mechanistic model to dissect the dynamics of synaptic vesicle fusion, and compare the feedback effects of DAT‐1 with the dopamine auto‐receptor. Our experimental results and the mechanistic model are of potential broader significance, as similar dynamics are likely to be used by other synaptic modulators including membrane transporters for other neurotransmitters across species.

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Increased dopaminergic neurotransmission results in ethanol dependent sedative behaviors in Caenorhabditis elegans

Cited by 17 publications

References 108 publications

Transcriptional analysis of the response of C. elegans to ethanol exposure

Transcriptional analysis of the response of C. elegans to ethanol exposure

Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs

The dopamine membrane transporter plays an active modulatory role in synaptic dopamine homeostasis

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