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.
Highlights
The impact of addiction on our society is profound and by all accounts is increasing
Work from our group and others shows that the effects of substances of abuse (SOAs) on neurobiology and behavior is phylogenetically ancient, suggesting that invertebrates possess some of the mechanisms that underlie addiction
We have discovered that this EtOH preference response can be selectively blocked by pretreatment with the pan-opioid receptor antagonist, a treatment for alcohol and opiate use disorders, naltrexone, which is consistent with the recent discovery of an opioid receptor system in C. elegans that mediates responses to both appetitive stimuli (Cheong et al, 2015) as well as nociception (Mills et al, 2016)
Summary
The impact of addiction on our society is profound and by all accounts is increasing. Behavioral measures used to model and study human addiction in animals (cf., Bell and Rahman, 2016) in conjunction with functional neurobiological studies have provided us with an understanding of basic reward circuitry (Koob and Volkow, 2010). In Drosophila melanogaster, ethanol (EtOH) conditioning and self-administration paradigms have demonstrated that flies develop conditioned preference responses to cues previously paired with EtOH (Kaun et al, 2011). These data show that even simple invertebrate animals can model what are widely considered to be highly complex behaviors. This should not be surprising as behavioral models using invertebrates have played a key role in discovering the underlying molecular mechanisms that provide the basis for learning and memory (Kandel, 2001)
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