期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 560, 期 -, 页码 192-198出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.05.002
关键词
Delta-opioid receptor; Excitatory synaptic transmission; Neuronal excitability; Prelimbic medial prefrontal cortex
资金
- Cyclic Innovation for Clinical Empowerment from the Japan Agency for Medical Research and Development (AMED) [17pc0101018h0001]
- KAKENHI, from the Japan Society for the Promotion of Science (JSPS) [17K10286, 20K06930]
- Grants-in-Aid for Scientific Research [17K10286, 20K06930] Funding Source: KAKEN
The study showed that KNT-127 suppressed glutamate release from the presynaptic site in the PL-PFC, reducing neuronal excitability. This suggests that the inhibitory effects of KNT-127 on PL-PFC activity may contribute to its anxiolytic-like effects.
The medial prefrontal cortex (mPFC) plays a vital role in the processing of emotional events. It has been shown that activation of the glutamatergic transmission in prelimbic subregion of the mPFC (PL-PFC) evoked anxiety-like behavior in rodents. We previously reported that local perfusion of a selective agonist to delta-opioid receptor (DOP), KNT-127, attenuated the veratrine-induced elevation of extra cellular glutamate in the PL-PFC and anxiety-like behavior in mice. These results suggested the possibility that KNT-127 suppresses glutamate release from the presynaptic site in the PL-PFC. To examine this possibility directly, we performed whole-cell patch-clamp recording from principal neurons in the PLPFC and examined the spontaneous and electrically-evoked excitatory postsynaptic currents (EPSC)s. We found that bath application of KNT-127 significantly decreased the frequency of spontaneous and miniature EPSCs. Conversely, amplitude, rise time, and decay time of spontaneous and miniature EPSCs were not affected by bath application of KNT-127. Also, KNT-127 increased paired-pulse ratios of electrically-evoked EPSCs in the PL-PFC principal neurons tested. Further, we analyzed the firing properties of pyramidal neurons in the PL-PFC and found that KNT-127 treatment significantly reduced the number of action potentials and firing threshold. These results suggested that KNT-127 suppresses glutamatergic synaptic transmission by inhibiting glutamate release from the presynaptic site and reduces neuronal excitability in the mouse PL-PFC. We propose the possibility that these suppressing effects of KNT-127 on PL-PFC activity are part of the underlying mechanisms of its anxiolytic-like effects. (c) 2021 Elsevier Inc. All rights reserved.
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