The delta opioid receptor agonist KNT-127 in the prelimbic medial prefrontal cortex attenuates veratrine-induced anxiety-like behaviors in mice
| Autor: | Akiyoshi Saitoh, Mitsuhiko Yamada, Satoshi Suzuki, Jun-Ichiro Oka, Misa Yamada, Akinobu Soda, Masanori Ohashi, Hiroshi Nagase |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Agonist Male Microdialysis medicine.drug_class Glutamic Acid Prefrontal Cortex Pharmacology Neurotransmission Anxiety Motor Activity Synaptic Transmission Open field δ-opioid receptor Veratrine 03 medical and health sciences Behavioral Neuroscience Glutamatergic Mice 0302 clinical medicine Receptors Opioid delta medicine Animals Prefrontal cortex Behavior Animal Chemistry Glutamate receptor Amygdala Mice Inbred C57BL 030104 developmental biology Anti-Anxiety Agents Morphinans Proto-Oncogene Proteins c-fos 030217 neurology & neurosurgery |
| Zdroj: | Behavioural brain research. 336 |
| ISSN: | 1872-7549 |
| Popis: | We previously reported that systemic administration of the selective delta opioid receptor (DOP) agonist KNT-127 produces potent anxiolytic-like effects in rats. Although a higher distribution pattern of DOPs was reported in the prelimbic medial prefrontal cortex (PL-PFC) of rodents, the role of DOPs in PL-PFC and in anxiolytic-like effects have not been well examined. Recently, we demonstrated that activation of PL-PFC with the sodium channel activator veratrine increases glutamatergic neurotransmission and produces anxiety-like behaviors in mice. Therefore, we investigated the effects of co-perfusion with KNT-127 in PL-PFC on veratrine-induced anxiety-like behaviors in mice. We also simultaneously measured extracellular glutamate and GABA levels. In addition, we assessed the effect of KNT-127 on the expression of c-Fos in sub-regions of the amygdala. Extracellular glutamate levels were measured in seven-week-old male C57BL/6N mice using an in vivo microdialysis-HPLC/ECD system, and behaviors were assessed simultaneously in an open field test. Basal levels of glutamate were measured by collecting samples every 10min for 60min. The drug-containing medium was perfused for 30min, and the open field test was performed during the last 10min of drug perfusion. After drug treatments, the perfusion was switched from drug-containing medium to control medium without drugs and samples were collected for another 90min. KNT-127 co-perfusion completely diminished veratrine-induced anxiety-like behaviors and attenuated the veratrine-induced increase in extracellular glutamate levels in PL-PFC. Interestingly, KNT-127 perfusion alone in PL-PFC did not affect anxiety-like behaviors. Local perfusion of veratrine in PL-PFC induced c-Fos immunoreactivity in sub-regions of amygdala. Co-perfusion of KNT-127 diminished c-Fos expression. Here we demonstrate that the DOP agonist KNT-127 in PL-PFC attenuates veratrine-induced anxiety-like behaviors in mice. These effects may be caused by the presynaptic suppression of activated glutamatergic transmission in PL-PFC, which projects to sub-regions of the amygdala. We propose that compounds like KNT-127, which inhibit glutamatergic transmission in PL-PFC, are candidates for novel anxiolytics. |
| Databáze: | OpenAIRE |
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