'Unexciting' an anxious brain: Novel drug reduces anxiety-like behavior in mice

Anxiety is often described as fear, dread and restlessness. It is an acceptable response to stressful situations. An anxiety disorder is a condition that causes heightened anxiety. This is what thousands of people experience every day. Anxiety disorder can cause debilitating anxiety and fear, even without immediate danger. Although extensive research has produced a wealth of information and effective drugs such as selective serotonin receptor inhibitors have been developed to treat anxiety disorder, there is still much to learn about the condition.This line of research is nothing new for a group of Japanese researchers at the University of Tsukuba and Tokyo University of Science. They used KNT-127, a drug that activates specific receptors in the brain called "delta opioids receptors". KNT-127 was found to decrease anxiety-like behavior in mice by the researchers. KNT-127 reduced the excitatory neurotransmitter glutamate in extracellular regions of the brain. This part of the brain controls many emotional states and is known as the "prelimbic region of the medial prefrontal cortex (PL-PFC). This phenomenon was further investigated by the researchers in a new study that was published in Biochemical & Biophysical Research Communication.Professor Akiyoshi Saidoh from Tokyo University of Science and corresponding author of the study says there's good reason to have studied the glutamate levels in PL-PFC. He said, "The medial frontal cortex (mPFC), plays an important role in processing emotional events." In rodents, anxiety-like behavior was evoked by activating the glutamatergic transmission of PL-PFC.Professor Saitoh conducted electrophysiological studies on mice at the single-neuron scale with his colleagues. In the PL-PFC, mice with anxious behavior were induced to show anxiety. The team measured the spontaneous excitatory currents in the glutamate-releasing region of several important neurons.The results of neurons treated with KNT127 showed that glutamate release was decreased at the PL–PFC synapses. This excitatory neurotransmitter relays data from one neuron, and at the synapse area, brain activity was also reduced. The team discovered that KNT127 treatment caused the neurons of the PL-PFC to be less excitable. These findings were attributed to the anxiolytic properties of KNT127, according to researchers.This study suggests a novel route and a novel candidate drug for the treatment of anxiety disorder. Dr. Daisuke Nagada from Tokyo University of Science commented on the clinical potential of KNT-127 drugs. He said, "There is a need to develop new therapeutic agents with different mechanisms of action than existing drugs." This study is expected to result in the development of evidence-based antipsychotics that target opioid delta receptors.The world can now hope that innovative anxiolytic drugs will soon hit the market, based on the promising results of this study!