title: SEB-3, a CRF receptor-like GPCR, regulates locomotor activity states, stress responses and ethanol tolerance in Caenorhabditis elegans.
abstract: The CRF (corticotropin-releasing factor) system is a key mediator of the stress response. Alterations in CRF signaling have been implicated in drug craving and ethanol consumption. The development of negative reinforcement via activation of brain stress systems has been proposed as a mechanism that contributes to alcohol dependence. Here, we isolated a gain-of-function allele of seb-3, a CRF receptor-like GPCR in Caenorhabditis elegans, providing an in vivo model of a constitutively activated stress system. We also characterized a loss-of-function allele of seb-3 and showed that SEB-3 positively regulates a stress response that leads to an enhanced active state of locomotion, behavioral arousal and tremor. SEB-3 also contributed to acute tolerance to ethanol and to the development of tremor during ethanol withdrawal. Furthermore, we found that a specific CRF(1)  receptor antagonist reduced acute functional tolerance to ethanol in mice. These findings demonstrate functional conservation of the CRF system in responses to stress and ethanol in vertebrates and invertebrates.
authors.affiliation: The Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, Emeryville, CA, USA. cjee@bio.tamu.edu
authors.forename: C
authors.initials: C
authors.lastname: Jee
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: J P
authors.initials: JP
authors.lastname: Lim
authors.forename: D
authors.initials: D
authors.lastname: Parry
authors.forename: R O
authors.initials: RO
authors.lastname: Messing
authors.forename: S L
authors.initials: SL
authors.lastname: McIntire
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001143:Arousal / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D018869:Heat-Shock Response / Q000235:genetics*; D008124:Locomotion / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological; D013375:Substance Withdrawal Syndrome / Q000235:genetics*; D014202:Tremor / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; D043562:Receptors, G-Protein-Coupled; C582721:SEB-3 protein, C elegans; D000431:Ethanol