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.

Drug-Induced Conditioned Place Preference and Its Practical Use in Substance Use Disorder Research

“…Conditioned place preference (CPP) was developed as a technique to assess the reinforcing properties of opioid drugs (Rossi and Reid, 1976 ; Katz and Gormezano, 1979 ; Mucha and Iversen, 1984 ). Now, CPP is widely used to test context associations based on the rewarding properties of an unconditioned stimulus in many organisms including, rodents (Lu et al, 2005 ; Akbarabadi et al, 2018 ; Cunningham, 2019 ), flies (Kaun et al, 2011 ), C. elegans (Musselman et al, 2012 ; Engleman et al, 2018 ), planaria (Hutchinson et al, 2015 ; Mohammed Jawad et al, 2018 ; Adams and Byrne, 2019 ; Phelps et al, 2019 ), primates (Wang et al, 2012 ; Borges et al, 2015 ; Yan et al, 2015 ; Wu et al, 2016 ), and humans (Thewissen et al, 2006 ; Childs and De Wit, 2009 , 2013 , 2016 ). Although a widely used behavioral model, CPP is a complex behavior that incorporates Pavlovian learning, memory, and motivated behaviors.…”

Caenorhabditis elegans as a model system to identify therapeutics for alcohol use disorders

“…elegans. However, varenicline pre-exposure has been shown to reduce chemotaxis to nicotine in C. elegans [31,33].…”

“…The current findings build on these studies with some essential new methods to evaluate EtOH behavioral responses dependent on choice behavior as opposed to conditions of forced EtOH exposure. C. elegans show responses to various drugs of abuse, including stimulants and EtOH [9,14,[31][32][33]. C. elegans have long been known to show chemotaxis toward EtOH [14].…”

Acetylcholine Signaling Genes are Required for Cocaine-Stimulated Egg Laying inCaenorhabditis elegans

“…In an effort to add to the current cocaine abuse models available in C. elegans (23)(24)(25), we set out to observe any strong phenotypes that may result from acute exposure of WT C. elegans to cocaine. Our initial observations determined that WT worms cultured on plates containing cocaine overnight showed several behavioral differences compared to untreated controls, including a previously reported modulation of locomotion (23).…”