title: Social feeding in Caenorhabditis elegans is modulated by antipsychotic drugs and calmodulin and may serve as a protophenotype for asociality.
abstract: Here, we define a protophenotype as an endophenotype that has been conserved during evolution. Social feeding in Caenorhabditis elegans may be an example of a protophenotype related to asociality in schizophrenia. It is regulated by the highly conserved neuropeptide Y receptor, NPR-1, and we speculated that social feeding should be affected by antipsychotic drugs. The social feeding strain, npr-1(g320), was exposed to antipsychotic drugs, dopamine or calmodulin antagonists on plates with bacterial lawns, and the number of aggregates on the plates was counted as a measure of social feeding. First-generation antipsychotics, chlorpromazine, trifluoperazine, fluphenazine, and haloperidol, and the second-generation drug, olanzapine, inhibited social feeding. Dopamine accelerated aggregation, whereas selective D2 dopamine receptor antagonists, sulpiride and raclopride, were inhibitory. Calmodulin antagonists effectively inhibited social feeding, as did RNAi knockdown of calmodulin (cmd-1) expression. In addition, gap junction inhibitors prevented aggregation, which is consistent with the hub-and-spoke arrangement of neurons that regulate social feeding via functional gap junctions. The studies described here revealed novel connections between dopaminergic signaling, the NPY receptor, calmodulin, and gap junctions in the regulation of social behavior in C. elegans. These pathways are evolutionarily-conserved, and have also been implicated in the pathogenesis of schizophrenia.
authors.affiliation: Department of Psychiatry, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA, USA. Electronic address: ddwyer@lsuhsc.edu.
authors.forename: Donard S
authors.initials: DS
authors.lastname: Dwyer
authors.affiliation: Department of Psychiatry, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Poonam
authors.initials: P
authors.lastname: Awatramani
authors.affiliation: Department of Psychiatry, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Thakur
authors.affiliation: Department of Psychiatry, Mount Sinai Beth Israel Medical Center, New York, NY, USA.
authors.forename: Ramya
authors.initials: R
authors.lastname: Seeni
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Aamodt
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D014150:Antipsychotic Agents / Q000494:pharmacology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects*; D017629:Gap Junctions / Q000187:drug effects / Q000235:genetics; D007093:Imidazoles / Q000494:pharmacology; D010641:Phenotype; D034741:RNA, Small Interfering / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D012919:Social Behavior; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D029742:Caenorhabditis elegans Proteins; D002147:Calmodulin; D004791:Enzyme Inhibitors; D007093:Imidazoles; C468272:NPR-1 protein, C elegans; D034741:RNA, Small Interfering; D017476:Receptors, Neuropeptide Y; D013449:Sulfonamides; C031938:calmidazolium; C017967:W 7; D004298:Dopamine
keywords: Antipsychotic drugs; Asociality; Calmodulin; Dopamine; Endophenotypes; Gap junctions; Schizophrenia