Caenorhabditis elegans show preference for stimulants and potential as a model organism for medications screening

Eric Engleman, Kevin B. Steagall, Kristin E. Bredhold, Michaela Breach, Hannah L. Kline, Richard Bell, Simon N. Katner, Bethany S. Neal-Beliveau

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The nematode Caenorhabditis elegans (C. elegans) is a popular invertebrate model organism to study neurobiological disease states. This is due in part to the intricate mapping of all neurons and synapses of the entire animal, the wide availability of mutant strains, and the genetic and molecular tools that can be used to manipulate the genome and gene expression. We have shown that, C. elegans develops a conditioned preference for cues that had previously been paired with either cocaine or methamphetamine exposure that is dependent on dopamine neurotransmission, similar to findings using place conditioning with rats and mice. In the current study, we show C. elegans also display a preference for, and self-exposure to, cocaine and nicotine. This substance of abuse (SOA) preference response can be selectively blocked by pretreatment with naltrexone and is consistent with the recent discovery of an opioid receptor system in C. elegans. In addition, pre-exposure to the smoking cessation treatment varenicline also inhibits self-exposure to nicotine. Exposure to concentrations of treatments that inhibit SOA preference/self-exposure did not induce any significant inhibition of locomotor activity or affect food or benzaldehyde chemotaxis. These data provide predictive validity for the development of high-throughput C. elegans behavioral medication screens. These screens could enable fast and accurate generation of data to identify compounds that may be effective in treating human addiction. The successful development and validation of such models would introduce powerful and novel tools in the search for new pharmacological treatments for substance use disorders, and provide a platform to study the mechanisms that underlie addictions.

Original languageEnglish (US)
Article number1200
JournalFrontiers in Physiology
Volume9
Issue numberAUG
DOIs
StatePublished - Aug 30 2018

Fingerprint

Caenorhabditis elegans
Substance-Related Disorders
Nicotine
Cocaine
Naltrexone
Withholding Treatment
Methamphetamine
Opioid Receptors
Chemotaxis
Smoking Cessation
Invertebrates
Locomotion
Synaptic Transmission
Synapses
Cues
Molecular Biology
Dopamine
Genome
Pharmacology
Gene Expression

Keywords

  • Addiction research
  • Cocaine
  • High-throughput screening assays
  • Invertebrate models
  • Nicotine
  • Self-administration models

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Caenorhabditis elegans show preference for stimulants and potential as a model organism for medications screening. / Engleman, Eric; Steagall, Kevin B.; Bredhold, Kristin E.; Breach, Michaela; Kline, Hannah L.; Bell, Richard; Katner, Simon N.; Neal-Beliveau, Bethany S.

In: Frontiers in Physiology, Vol. 9, No. AUG, 1200, 30.08.2018.

Research output: Contribution to journalArticle

Engleman, Eric ; Steagall, Kevin B. ; Bredhold, Kristin E. ; Breach, Michaela ; Kline, Hannah L. ; Bell, Richard ; Katner, Simon N. ; Neal-Beliveau, Bethany S. / Caenorhabditis elegans show preference for stimulants and potential as a model organism for medications screening. In: Frontiers in Physiology. 2018 ; Vol. 9, No. AUG.
@article{19d99611f2a44f2ea93543586472a83f,
title = "Caenorhabditis elegans show preference for stimulants and potential as a model organism for medications screening",
abstract = "The nematode Caenorhabditis elegans (C. elegans) is a popular invertebrate model organism to study neurobiological disease states. This is due in part to the intricate mapping of all neurons and synapses of the entire animal, the wide availability of mutant strains, and the genetic and molecular tools that can be used to manipulate the genome and gene expression. We have shown that, C. elegans develops a conditioned preference for cues that had previously been paired with either cocaine or methamphetamine exposure that is dependent on dopamine neurotransmission, similar to findings using place conditioning with rats and mice. In the current study, we show C. elegans also display a preference for, and self-exposure to, cocaine and nicotine. This substance of abuse (SOA) preference response can be selectively blocked by pretreatment with naltrexone and is consistent with the recent discovery of an opioid receptor system in C. elegans. In addition, pre-exposure to the smoking cessation treatment varenicline also inhibits self-exposure to nicotine. Exposure to concentrations of treatments that inhibit SOA preference/self-exposure did not induce any significant inhibition of locomotor activity or affect food or benzaldehyde chemotaxis. These data provide predictive validity for the development of high-throughput C. elegans behavioral medication screens. These screens could enable fast and accurate generation of data to identify compounds that may be effective in treating human addiction. The successful development and validation of such models would introduce powerful and novel tools in the search for new pharmacological treatments for substance use disorders, and provide a platform to study the mechanisms that underlie addictions.",
keywords = "Addiction research, Cocaine, High-throughput screening assays, Invertebrate models, Nicotine, Self-administration models",
author = "Eric Engleman and Steagall, {Kevin B.} and Bredhold, {Kristin E.} and Michaela Breach and Kline, {Hannah L.} and Richard Bell and Katner, {Simon N.} and Neal-Beliveau, {Bethany S.}",
year = "2018",
month = "8",
day = "30",
doi = "10.3389/fphys.2018.01200",
language = "English (US)",
volume = "9",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers Research Foundation",
number = "AUG",

}

TY - JOUR

T1 - Caenorhabditis elegans show preference for stimulants and potential as a model organism for medications screening

AU - Engleman, Eric

AU - Steagall, Kevin B.

AU - Bredhold, Kristin E.

AU - Breach, Michaela

AU - Kline, Hannah L.

AU - Bell, Richard

AU - Katner, Simon N.

AU - Neal-Beliveau, Bethany S.

PY - 2018/8/30

Y1 - 2018/8/30

N2 - The nematode Caenorhabditis elegans (C. elegans) is a popular invertebrate model organism to study neurobiological disease states. This is due in part to the intricate mapping of all neurons and synapses of the entire animal, the wide availability of mutant strains, and the genetic and molecular tools that can be used to manipulate the genome and gene expression. We have shown that, C. elegans develops a conditioned preference for cues that had previously been paired with either cocaine or methamphetamine exposure that is dependent on dopamine neurotransmission, similar to findings using place conditioning with rats and mice. In the current study, we show C. elegans also display a preference for, and self-exposure to, cocaine and nicotine. This substance of abuse (SOA) preference response can be selectively blocked by pretreatment with naltrexone and is consistent with the recent discovery of an opioid receptor system in C. elegans. In addition, pre-exposure to the smoking cessation treatment varenicline also inhibits self-exposure to nicotine. Exposure to concentrations of treatments that inhibit SOA preference/self-exposure did not induce any significant inhibition of locomotor activity or affect food or benzaldehyde chemotaxis. These data provide predictive validity for the development of high-throughput C. elegans behavioral medication screens. These screens could enable fast and accurate generation of data to identify compounds that may be effective in treating human addiction. The successful development and validation of such models would introduce powerful and novel tools in the search for new pharmacological treatments for substance use disorders, and provide a platform to study the mechanisms that underlie addictions.

AB - The nematode Caenorhabditis elegans (C. elegans) is a popular invertebrate model organism to study neurobiological disease states. This is due in part to the intricate mapping of all neurons and synapses of the entire animal, the wide availability of mutant strains, and the genetic and molecular tools that can be used to manipulate the genome and gene expression. We have shown that, C. elegans develops a conditioned preference for cues that had previously been paired with either cocaine or methamphetamine exposure that is dependent on dopamine neurotransmission, similar to findings using place conditioning with rats and mice. In the current study, we show C. elegans also display a preference for, and self-exposure to, cocaine and nicotine. This substance of abuse (SOA) preference response can be selectively blocked by pretreatment with naltrexone and is consistent with the recent discovery of an opioid receptor system in C. elegans. In addition, pre-exposure to the smoking cessation treatment varenicline also inhibits self-exposure to nicotine. Exposure to concentrations of treatments that inhibit SOA preference/self-exposure did not induce any significant inhibition of locomotor activity or affect food or benzaldehyde chemotaxis. These data provide predictive validity for the development of high-throughput C. elegans behavioral medication screens. These screens could enable fast and accurate generation of data to identify compounds that may be effective in treating human addiction. The successful development and validation of such models would introduce powerful and novel tools in the search for new pharmacological treatments for substance use disorders, and provide a platform to study the mechanisms that underlie addictions.

KW - Addiction research

KW - Cocaine

KW - High-throughput screening assays

KW - Invertebrate models

KW - Nicotine

KW - Self-administration models

UR - http://www.scopus.com/inward/record.url?scp=85052815087&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052815087&partnerID=8YFLogxK

U2 - 10.3389/fphys.2018.01200

DO - 10.3389/fphys.2018.01200

M3 - Article

AN - SCOPUS:85052815087

VL - 9

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - AUG

M1 - 1200

ER -