title: Dopamine receptors antagonistically regulate behavioral choice between conflicting alternatives in C. elegans.
abstract: Caenorhabditis elegans is a useful model to study the neuronal or molecular basis for behavioral choice, a specific form of decision-making. Although it has been implied that both D1-like and D2-like dopamine receptors may contribute to the control of decision-making in mammals, the genetic interactions between D1-like and D2-like dopamine receptors in regulating decision-making are still largely unclear. In the present study, we investigated the molecular control of behavioral choice between conflicting alternatives (diacetyl and Cu2+) by D1-like and D2-like dopamine receptors and their possible genetic interactions with C. elegans as the assay system. In the behavioral choice assay system, mutation of dop-1 gene encoding D1-like dopamine receptor resulted in the enhanced tendency to cross the Cu2+ barrier compared with wild-type. In contrast, mutations of dop-2 or dop-3 gene encoding D2-like dopamine receptor caused the weak tendency to cross the Cu2+ barrier compared with wild-type. During the control of behavioral choice, DOP-3 antagonistically regulated the function of DOP-1. The behavioral choice phenotype of dop-2; dop-1dop-3 triple mutant further confirmed the possible antagonistic function of D2-like dopamine receptor on D1-like dopamine receptor in regulating behavioral choice. The genetic assays further demonstrate that DOP-3 might act through Gαo signaling pathway encoded by GOA-1 and EGL-10, and DOP-1 might act through Gαq signaling pathway encoded by EGL-30 and EAT-16 to regulate the behavioral choice. DOP-1 might function in cholinergic neurons to regulate the behavioral choice, whereas DOP-3 might function in GABAergic neurons, RIC, and SIA neurons to regulate the behavioral choice. In this study, we provide the genetic evidence to indicate the antagonistic relationship between D1-like dopamine receptor and D2-like dopamine receptor in regulating the decision-making of animals. Our data will be useful for understanding the complex functions of dopamine receptors in regulating decision-making in animals.
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Daoyong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Yinxia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002755:Choice Behavior; D004298:Dopamine / Q000378:metabolism; D009154:Mutation; D020710:RGS Proteins / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C494134:DOP-3 protein, C elegans; C488450:Dop-1 protein, C elegans; C105577:EGL-10 protein, C elegans; D020710:RGS Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C477462:dop-2 protein, C elegans; D004298:Dopamine