In humans, activation or blockade of cannabinoid receptors increases or decreases food intake, respectively ( Colombo et al., 1998 Simiand et al., 1998). The mammalian ECS is composed of AEA (N-arachidonoylethanolamine) and 2-AG (2-Arachidonoylglycerol), their receptors, including CB1 and CB2, synthetic enzymes, and degradative enzymes. Integration of energy-state cues, chemosensory information about food, and food intake is mediated, in part, by the endocannabinoid system (ECS) ( Matias & Di Marzo, 2007 Soria-Gómez et al., 2014). An animal must take into account its hunger state and the available food in the environment to decide whether, where, and how much to feed. Maintenance of energy balance is critical to an animal’s survival. Instead, it appears that AEA modulates AWC by activating one or more npr-19-expressing neurons that release a diffusible neuromodulator to which AWC is sensitive.
Although AEA’s effect could be mediated by NPR-19-expressing neurons presynaptic to AWC, nearly complete elimination of fast synaptic transmission, via the mutation unc-13(e51), had no effect on modulation. In a GFP expression analysis, we found that npr-19 is expressed in approximately 21 neuron classes but, surprisingly, not in AWC. Consistent with this finding, calcium imaging revealed that AEA bidirectionally modulates AWC activity, increasing its responses to strongly preferred food and decreasing its response for weakly preferred food. Deletion of the olfactory neuron AWC, which directs chemotaxis to food, abolishes hedonic amplification. We also found that deletion of the putative CB1 homolog, npr-19, eliminates hedonic amplification, which can be rescued by expression of wild type npr-19 or human CB1, establishing a humanized worm for cannabinoid signaling studies. Furthermore, AEA acts bidirectionally, increasing consumption of strongly preferred bacteria while decreasing consumption of weakly preferred bacteria. We found that exposure to AEA increases the worms’ preference for strongly preferred (more palatable) bacteria over weakly preferred (less palatable) bacteria, mimicking hedonic amplification in mammals. elegans, an omnivorous bacterivore, as a model in which to investigate the neurophysiology of hedonic amplification. For example, cannabinoids can increase preference for more palatable, calorically dense food: a response called hedonic amplification, colloquially known as “the munchies.” In mammals, cannabinoids can increase sensitivity to odors and sweet tastes, which may underlie amplification. The mammalian endocannabinoid system, comprised of the endocannabinoids AEA (N-arachidonoyl-ethanolamine) and 2-AG (2-Arachidonoylglycerol), their receptors, CB1 and CB2, and their metabolic enzymes, is believed to integrate internal energy state and external food cues to modulate feeding.
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