The BigLEN-GPR171 Peptide Receptor System Within the Basolateral Amygdala Regulates Anxiety-Like Behavior and Contextual Fear Conditioning
| Autor: | Lakshmi A. Devi, Ivone Gomes, Mihaly Mezei, Roger L. Clem, Erin N. Bobeck, Kirstie A. Cummings, Darlene Aparecida Pena |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Models Molecular Neuropeptide Mice Transgenic Molecular neuroscience CHO Cells Anxiety Motor Activity Amygdala Receptors G-Protein-Coupled Tissue Culture Techniques 03 medical and health sciences 0302 clinical medicine Cricetulus Conditioning Psychological medicine Animals Agouti-Related Protein Fear conditioning Receptor Pharmacology Neurons Gene knockdown Basolateral Nuclear Complex Neuropeptides Arcuate Nucleus of Hypothalamus Fear Feeding Behavior Rats Mice Inbred C57BL Psychiatry and Mental health 030104 developmental biology medicine.anatomical_structure Systemic administration Original Article Psychology Neuroscience 030217 neurology & neurosurgery Basolateral amygdala |
| Popis: | Studies show that neuropeptide-receptor systems in the basolateral amygdala (BLA) play an important role in the pathology of anxiety and other mood disorders. Since GPR171, a recently deorphanized receptor for the abundant neuropeptide BigLEN, is expressed in the BLA, we investigated its role in fear and anxiety-like behaviors. To carry out these studies we identified small molecule ligands using a homology model of GPR171 to virtually screen a library of compounds. One of the hits, MS0021570_1, was identified as a GPR171 antagonist based on its ability to block (i) BigLEN-mediated activation of GPR171 in heterologous cells, (ii) BigLEN-mediated hyperpolarization of BLA pyramidal neurons, and (iii) feeding induced by DREADD-mediated activation of BigLEN containing AgRP neurons in the arcuate nucleus. The role of GPR171 in anxiety-like behavior or fear conditioning was evaluated following systemic or intra-BLA administration of MS0021570_1, as well as following lentiviral-mediated knockdown of GPR171 in the BLA. We find that systemic administration of MS0021570_1 attenuates anxiety-like behavior while intra-BLA administration or knockdown of GPR171 in the BLA reduces anxiety-like behavior and fear conditioning. These results indicate that the BigLEN-GPR171 system plays an important role in these behaviors and could be a novel target to develop therapeutics to treat psychiatric disorders. |
| Databáze: | OpenAIRE |
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