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GPR171 in the Basolateral Amygdala Regulates Stress and Reward‐Related Behaviors
Author(s) -
Bobeck Erin,
Pena Darlene,
Gomes Ivone,
Fujita Wakako,
Devi Lakshmi
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1265.9
Subject(s) - basolateral amygdala , amygdala , gene knockdown , conditioned place preference , anxiety , small hairpin rna , receptor , hypothalamus , psychology , chemistry , neuroscience , neuropeptide , medicine , addiction , gene , psychiatry , biochemistry
Recently we deorphanized GPR171, a hypothalamic G protein‐coupled receptor, as the receptor for the abundant neuropeptide, Big‐LEN. By virtual screening of a library of small molecules, we identified compounds that selectively target GPR171. Using these compounds we found that the activation of GPR171 within the hypothalamus regulates feeding. Additional characterization of the distribution of GPR171 revealed high expression in the basolateral amygdala. This led us to explore a role for GPR171 in various stress and reward‐related behaviors using lentiviral shRNA‐mediated knockdown of GPR171. While decreases in expression of GPR171 in the basolateral amygdala had a minor or no effect on anxiety and depression, the decrease in expression had a major effect on fear learning and morphine conditioned place preference. In addition, we investigated these behaviors using GPR171 selective ligands and found a reduction in anxiety. Interestingly, we also find that mice subjected to repeated stress show an increase in GPR171 mRNA. Together, these results suggest a role for GPR171 in stress and reward‐related behaviors within the amygdala. Support or Funding Information This work was supported in part by NIH grants NS026880 and DA019521 to L.A.D and a NIDA postdoctoral training grant DA007135 to E.N.B.