Journal article
Disruption of Akt signaling decreases dopamine sensitivity in modulation of inhibitory synaptic transmission in rat prefrontal cortex
Neuropharmacology, v 108, pp 403-414
Sep 2016
PMID: 27163190
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Akt is a serine/threonine kinase, which is dramatically reduced in the prefrontal cortex (PFC) of patients with schizophrenia, and a deficiency in Akt1 results in PFC function abnormalities. Although the importance of Akt in dopamine (DA) transmission is well established, how impaired Akt signaling affects the DA modulation of synaptic transmission in the PFC has not been characterized. Here we show that Akt inhibitors significantly decreased receptor sensitivity to DA by shifting DA modulation of GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in prefrontal cortical neurons. Akt inhibition caused a significant decrease in synaptic dopamine D2 receptor (D2R) levels with high-dose DA exposure. In addition, Akt inhibition failed to affect DA modulation of IPSCs after blockade of β-arrestin 2. β-arrestin 2-mediated interaction of clathrin with D2R was enhanced by co-application of a Akt inhibitor and DA. Taken together, the reduced response in DA modulation of inhibitory transmission mainly involved β-arrestin 2-dependent D2R desensitization.
Metrics
Details
- Title
- Disruption of Akt signaling decreases dopamine sensitivity in modulation of inhibitory synaptic transmission in rat prefrontal cortex
- Creators
- Yan-Chun Li - Department of Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USASha-Sha Yang - Department of Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USAWen-Jun Gao - Department of Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA. Electronic address: wgao@drexelmed.edu
- Publication Details
- Neuropharmacology, v 108, pp 403-414
- Publisher
- Elsevier; England
- Grant note
- R03 MH101578 / NIMH NIH HHS R01 MH085666 / NIMH NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000378953500040
- Scopus ID
- 2-s2.0-84969626550
- Other Identifier
- 991014878050804721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy