RRC ID 46371
Author Jee C, Lee J, Lim JP, Parry D, Messing RO, McIntire SL.
Title SEB-3, a CRF receptor-like GPCR, regulates locomotor activity states, stress responses and ethanol tolerance in Caenorhabditis elegans.
Journal Genes Brain Behav.
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.
Volume 12(2)
Pages 250-62
Published 2013-3
DOI 10.1111/j.1601-183X.2012.00829.x
PMID 22853648
PMC PMC3848202
MeSH 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
IF 3.157
Times Cited 12
C.elegans tm1848