Scientists from the Tokyo University of Science and FUJIMIC, Inc. have investigated the effects of ultrasound exposure in olfactory bulbectomized rats (rats lacking olfactory lobes, organs that regulate neurotransmission), which is a high validated animal model of depression. They’ve found that ultrasound had antidepressant-like effects in these animals, suggesting that olfactory bulbectomized rats might be an appropriate animal model to identify mechanisms underlying the effects of ultrasound exposure.
Ultrasound exposure improved depressive-like behavior in olfactory bulbectomized rats and reduced their plasma corticosterone levels. Image credit: Mary Theresa McLean.
In recent years, the effects of ultrasound on brain function have been studied intensively.
For example, several studies have shown that whole-body exposure to high-frequency ultrasound significantly increases brain activity in humans, including that in reward-related neural circuitry.
Indeed, ultrasonic exposure appears to be a non-invasive method for modulating brain activity related to consciousness.
However, little is known about the effects and effect mechanisms of ultrasound on emotional states, such as depression.
Furthermore, most studies on ultrasound exposure have been conducted on human subjects; therefore, molecular mechanisms have been difficult to elucidate.
“Since studies on ultrasound exposure have been primarily conducted on human subjects, we needed to establish robust animal models to elucidate underlying mechanisms using invasive techniques,” said senior author Professor Akiyoshi Saitoh, a researcher in the Department of Pharmacy at the Tokyo University of Science.
“In our current study, we have used olfactory bulbectomized rats to study the effects of ultrasound on neural activity and behavior.”
Initially, Professor Saitoh and colleagues exposed wild and olfactory bulbectomized rats to high-frequency (50 kHz) ultrasound vocalizations for 24 hours.
They then scored the rodents for hyperemotionality (agitation and anxiety-like behavior) by studying their responses to getting attacked, getting startled, facing a struggle, and initiating a fight.
They monitored plasma levels of the stress hormone corticosterone in the blood samples of these rats.
They also assessed anxiety-like behavior of the animals using the elevated plus maze, an approach which triggers behavioral anxiety in rats by exposing them to open spaces in a maze, and causes them to move to closed spaces.
Their findings revealed that olfactory bulbectomized rats exposed to ultrasound vocalizations had significantly lower hyperemotionality scores and lower plasma corticosterone levels than unexposed rats.
Furthermore, in olfactory bulbectomized rats with a higher latency initially. i.e., higher inclination to reach the open areas of the maze, ultrasound exposure significantly decreased their latency.
Similar effects were observed with artificial 50-kHz ultrasound.
“Our findings suggest that olfactory bulbectomized rats may be a useful animal model for investigating the effects of ultrasound exposure and mechanisms of influence,” Professor Saitoh said.
“Unlike drug therapy, ultrasound exposure is non-invasive and easy to use. An ultrasound based therapeutic device may therefore aid the treatment and prevention of mental disorders in patients while they go about their daily lives.”
“Let’s hope that these results pave the way for developing ultrasound exposure therapy as a novel treatment to help patients cope with stress and psychiatric disorders.”
The results were published in the journal NeuroReport.
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Tsugumi Yamauchi et al. 2022. High-frequency ultrasound exposure improves depressive-like behavior in an olfactory bulbectomized rat model of depression. NeuroReport 33 (10): 445-449; doi: 10.1097/WNR.0000000000001804
