RT Journal Article
SR Electronic
T1 β-arrestin-dependent ERK signaling positively correlates with reduced anxiety-like and conditioned fear-related behavior in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 790568
DO 10.1101/790568
A1 Mee Jung Ko
A1 Terrance Chiang
A1 Arbaaz M. Mukadam
A1 Grace E. Mulia
A1 Anna M. Gutridge
A1 Julia A. Chester
A1 Richard M. van Rijn
YR 2019
UL http://biorxiv.org/content/early/2019/10/02/790568.abstract
AB Exposure to anxiety- or fear-invoking stimuli initiate a convergence of executive actions orchestrated by multiple proteins and neurotransmitters across the brain. Dozens of G protein-coupled receptors (GPCRs) have been linked to regulation of fear and anxiety. GPCR signaling involves canonical G protein pathways but may also engage downstream kinases and effectors through β-arrestin scaffolds. Here, we investigate whether β-arrestin signaling is critical for the emotional regulation of anxiety-like and fear-related behavior. Using the δ-opioid receptor (δOR) as a model GPCR, we found that β-arrestin 2-dependent activation of extracellular signal–regulated kinases (ERK1/2) in the dorsal hippocampus and the amygdala are critical for δOR-induced anxiolytic-like effects. In contrast, G protein-mediated δOR signaling was associated with decreased ERK1/2 activity and increased fear-related behavior. Our results also suggest a potential contribution of β-arrestin 1 in fear-reducing effects. Overall, our findings highlight the significance of non-canonical β-arrestin signaling in the regulation of emotions.