Reductions in sensory response after prior exposure to a stimulus, such as adaptation or habituation, have been extensively studied in various animals. In contrast, the enhancement of animals'' sensory response after preexposure has been poorly studied, except in a few cases such as sensitization of pain in mammals and of gill-withdrawal reflex in Aplysia. We have reported that preexposure to a repulsive odor of 2-nonanone causes enhancement of avoidance behavior, rather than adaptation, to the odor in a food information-independent manner (Kimura and Katsura, the previous IWM and CeNeuro abstracts). Genetic analysis has revealed that mutations in the dopamine biosynthetic pathway, such as
cat-2,
cat-1,
cat-4 and
bas-1, but not
tph-1, significantly affected the enhancement 2-nonanone avoidance, suggesting the requirement of dopamine signaling for the enhancement. Here, we report that the D2-like dopamine receptor
dop-3 is required for the enhancement of 2-nonanone avoidance. First, we conducted a pharmacological analysis with dopamine receptor antagonists. In mammals, dopamine receptors are classified into D1- and D2-subtypes, which regulate intracellular signaling positively or negatively, respectively. We found that the D2-specific antagonist haloperidol and the D1/D2 antagonist loxapine, but not the D1-specific SCH23390, specifically suppressed the enhancement of preexposed animals, suggesting that D2-like dopamine receptor(s) are involved in the process. Further, we found that deletion mutations in D2-like receptor
dop-3 significantly affected the enhancement. Mutations in another D2-like receptor
dop-2 did not affect the phenotype, and the phenotype of the double mutants
dop-2;
dop-3 were similar to that of the
dop-3 single mutants. Taken together, these results suggest that the
dop-3 D2-like dopamine receptor plays a critical role in the enhancement of 2-nonanone avoidance.
dop-3 has been known to regulate the basal slowing response in the ventral cord motor neurons (Chase et al., Nat Neurosci, 2004). In the regulation of basal slowing response (Sawin, Neuron, 2000), as well as area-restricted search (Hills et al., J. Neurosci., 2004) and tap habituation (Kindt et al., Neuron, 2007), dopamine signals "the presence of food" in C. elegans. In contrast, the enhancement of 2-nonanone avoidance is independent of food information, suggesting that a
dop-3-dependent novel dopamine signaling regulates the behavioral plasticity of the animals.