RRC ID |
46371
|
著者 |
Jee C, Lee J, Lim JP, Parry D, Messing RO, McIntire SL.
|
タイトル |
SEB-3, a CRF receptor-like GPCR, regulates locomotor activity states, stress responses and ethanol tolerance in Caenorhabditis elegans.
|
ジャーナル |
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.
|
巻・号 |
12(2)
|
ページ |
250-62
|
公開日 |
2013-3-1
|
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 |
3.397
|
引用数 |
14
|
WOS 分野
|
BEHAVIORAL SCIENCES
NEUROSCIENCES
|
リソース情報 |
線虫 |
tm1848 |