SEB-3, a CRF receptor-like GPCR, regulates locomotor activity states, stress responses and ethanol tolerance in Caenorhabditis elegans

Genes Brain Behav. 2013 Mar;12(2):250-62. doi: 10.1111/j.1601-183X.2012.00829.x. Epub 2012 Sep 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Arousal / genetics
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Ethanol / blood
  • Ethanol / toxicity*
  • Heat-Shock Response / genetics*
  • Locomotion / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Receptors, Corticotropin-Releasing Hormone / genetics
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Receptors, Corticotropin-Releasing Hormone / physiology*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / physiology*
  • Stress, Physiological
  • Substance Withdrawal Syndrome / genetics*
  • Tremor / genetics


  • Caenorhabditis elegans Proteins
  • Receptors, Corticotropin-Releasing Hormone
  • Receptors, G-Protein-Coupled
  • SEB-3 protein, C elegans
  • Ethanol