A delta opioid receptor agonist, KNT-127, in the prelimbic medial prefrontal cortex attenuates glial glutamate transporter blocker-induced anxiety-like behavior in mice

Publication date: Available online 27 September 2018Source: Journal of Pharmacological SciencesAuthor(s): Akiyoshi Saitoh, Akinobu Soda, Shuhei Kayashima, Kazumi Yoshizawa, Jun-Ichiro Oka, Hiroshi Nagase, Mitsuhiko YamadaAbstractWe previously reported that systemic administration of a delta opioid receptor (DOP) agonist, KNT-127, produced a potent anxiolytic-like effect in rats. Interestingly, DOPs are highly distributed in the prelimbic medial prefrontal cortex (PL-PFC). In the present study, we investigated the effect of KNT-127 co-perfusion in the PL-PFC on anxiety-like behavior in mice, induced by a glial glutamate transporter inhibitor, (3S)-3-[[3-[[4-(Trifluoromethyl)benzoyl]amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA). Extracellular glutamate levels were measured in male C57BL/6N mice by in vivo microdialysis high-performance liquid chromatography/electrochemical detection, with behavior simultaneously assessed in the open field test. As expected, extracellular glutamate levels were significantly increased, and anxiety-like behavior was induced after local perfusion of TFB-TBOA in the PL-PFC. Uniquely, co-perfusion of KNT-127 in the PL-PFC diminished anxiety-like behavior induced by TFB-TBOA without affecting extracellular glutamate levels. Further, the effect of KNT-127 on anxiety-like behavior was antagonized by a selective DOP antagonist, naltrindole, suggesting that KNT-127 acts via DOPs. These findings do not support our preconceived hypothesis that KNT-127 in...
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research