Disruption of Akt signaling decreases dopamine sensitivity in modulation of inhibitory synaptic transmission in rat prefrontal cortex

NEUROPHARMACOLOGY

卷:108

Article

Li, Yan-Chun¹  Yang, Sha-Sha¹  Gao, Wen-Jun¹ 

[1] Drexel Univ, Coll Med, Dept Neurobiol & Anat, 2900 Queen Lane, Philadelphia, PA 19129 USA

关键词: Dopamine;    Dopamine receptors;    Inhibitory synaptic transmission;    Akt;    Prefrontal cortex;    Schizophrenia;   

DOI  :  10.1016/j.neuropharm.2016.05.002

来源: Elsevier

【 摘 要 】

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 GABA(A) 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 beta-arrestin 2. beta-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 beta-arrestin 2-dependent D2R desensitization. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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