Mutation of dop-1;dop-2;dop-3 in Caenorhabditis elegans Increases Nicotine Preference

Abstract

Nicotine addiction remains a prevalent issue across the globe. The nematode Caenorhabditis elegans (C. elegans) is a model organism to study nicotine addiction, with a nervous system that mirrors the human nervous system and a fully sequenced genome that can be easily manipulated. The receptors DOP 1-4 in C. elegans express human D1 and D2-like receptor properties. Whether receptors DOP 1, 2, and 3 affected nicotine preference was a focus of this study. Here, we examined the effect of inhibiting dop-1;dop-2;dop-3 expression in worms on nicotine preference and locomotion. Specifically, nicotine preference was examined at concentrations ranging from 0-500 mM at 10 and 30 minutes post-plating, and locomotion was examined through a body bend assay. Nicotine preference, irrespective of strain or time, increased as nicotine concentration increased. While knockout (KO) worms exhibited an equivalent preference to N2 wild-type (WT) 10 minutes post-plating, significant increases in nicotine preference were observed in KO relative to N2 WT at 30 minutes post-plating. Body bend assay confirmed that preference results were not due to differential locomotive activity. Results, when integrated with current information in the literature, indicated that DOP-3 is crucial for inhibitory regulation of nicotine preference, although further examination is needed. Identifying the specific role of each DOP receptor in nicotine preference may allow for the development of novel therapeutic strategies to treat nicotine addiction.