内側前頭前野におけるデルタオピオイド受容体を介したグルタミン酸作動性シナプス伝達修飾

抄録

It has been shown that activation of the glutamatergic transmission in the prelimbic region 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 extracellular glutamate in the PL-PFC and anxiety-like behavior in mice. These results suggested the possibility that KNT-127 suppresses glutamate release from presynaptic site in the PL-PFC. To confirm this, we performed whole-cell patch-clamp recording from pyramidal neurons in the PL-PFC, and examined the spontaneous and electrically-evoked excitatory post-synaptic currents (EPSC)s. We found that bath application of KNT-127 significantly suppressed frequency, but not amplitude of spontaneous and miniature EPSCs in a DOP-dependent manner. Also, KNT-127 increased paired-pulse ratios in the PL-PFC pyramidal neurons tested. Further, we analysed the firing properties of pyramidal neurons in the PL-PFC, and found that KNT-127 treatment significantly reduced the number of action potentials and rheobase. These results suggested that KNT-127 not only suppresses glutamatergic synaptic transmission by inhibiting glutamate release from presynaptic site, but also reduces cell excitability via DOP in the mouse PL-PFC.