RRC ID 76048
Author Salim C, Kan AK, Batsaikhan E, Patterson EC, Jee C.
Title Neuropeptidergic regulation of compulsive ethanol seeking in C. elegans.
Journal Sci Rep
Abstract Despite the catastrophic consequences of alcohol abuse, alcohol use disorders (AUD) and comorbidities continue to strain the healthcare system, largely due to the effects of alcohol-seeking behavior. An improved understanding of the molecular basis of alcohol seeking will lead to enriched treatments for these disorders. Compulsive alcohol seeking is characterized by an imbalance between the superior drive to consume alcohol and the disruption or erosion in control of alcohol use. To model the development of compulsive engagement in alcohol seeking, we simultaneously exploited two distinct and conflicting Caenorhabditis elegans behavioral programs, ethanol preference and avoidance of aversive stimulus. We demonstrate that the C. elegans model recapitulated the pivotal features of compulsive alcohol seeking in mammals, specifically repeated attempts, endurance, and finally aversion-resistant alcohol seeking. We found that neuropeptide signaling via SEB-3, a CRF receptor-like GPCR, facilitates the development of ethanol preference and compels animals to seek ethanol compulsively. Furthermore, our functional genomic approach and behavioral elucidation suggest that the SEB-3 regulates another neuropeptidergic signaling, the neurokinin receptor orthologue TKR-1, to facilitate compulsive ethanol-seeking behavior.
Volume 12(1)
Pages 1804
Published 2022-2-2
DOI 10.1038/s41598-022-05256-1
PII 10.1038/s41598-022-05256-1
PMID 35110557
PMC PMC8810865
MeSH Alcohol Drinking* Alcohol-Related Disorders* Animals Animals, Genetically Modified Avoidance Learning Behavior, Animal* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Choice Behavior Compulsive Behavior* Drug-Seeking Behavior* Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism* Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism* Signal Transduction
Resource
C.elegans tm1848