Chemosensory cue conditioning with stimulants in a Caenorhabditis elegans animal model of addiction.

The underlying molecular mechanisms of drug abuse and addiction behaviors are poorly understood. Caenorhabditis elegans (C. elegans) provide a simple, whole animal model with conserved molecular pathways well suited for studying the foundations of complex diseases. Historically, chemotaxis has been a measure used to examine sensory approach and avoidance behavior in worms. Chemotaxis can be modulated by previous experience, and cue-dependent conditioned learning has been demonstrated in C. elegans, but such conditioning with drugs of abuse has not been reported. Here we show that pairing a distinctive salt cue with a drug (cocaine or methamphetamine) results in a concentration-dependent change in preference for the cue that was paired with the drug during conditioning. Further, we demonstrate that pairing of either drug with a distinctive food type can also increase preference for the drug-paired food in the absence of the drug. Dopamine-deficient mutants did not develop drug-paired, cue-conditioned responses. The findings suggest that, like vertebrates, C. elegans display a conditioned preference for environments containing cues previously associated with drugs of abuse, and this response is dependent on dopamine neurotransmission. This model provides a new and powerful method to study the genetic and molecular mechanisms that mediate drug preference.