High-frequency ultrasound exposure improves depressive-like behavior in an olfactory bulbectomized rat model of depression

Abstract

Objectives According to previous studies, ultrasound exposure appears to be a noninvasive method for modulating brain activity related to cognition and consciousness; however, its effects on emotional states remain unclear. Therefore, an animal model is required in which the effects and effect mechanisms of ultrasound exposure can be investigated. Thus, we used olfactory bulbectomized rats as an animal model of depression and investigated their emotional state following ultrasound exposure. MethodsIn male Wistar/ST olfactory bulbectomized rats, hyperemotionality was evaluated according to hyperemotionality scoring and the scores before and after 24-h ultrasound exposure were compared. Elevated plus maze (EPM) tests were also conducted after 24-h ultrasound exposure, and blood samples were collected in which plasma corticosterone concentrations were measured. ResultsFollowing exposure to high-frequency (~50 kHz) ultrasound vocalizations (USVs) associated with the pleasant emotions of rats, the hyperemotionality scores of olfactory bulbectomized rats were significantly reduced. Additionally, the latency of the first entry into the open arm of the EPM was significantly decreased in USV-exposed olfactory bulbectomized rats, as were their plasma corticosterone levels. Furthermore, artificial ultrasound (50 kHz) at a similar frequency to that of USV also significantly decreased the hyperemotionality score of olfactory bulbectomized rats.Conclusions Ultrasound exposure improved depressive-like behavior in olfactory bulbectomized rats and reduced their plasma corticosterone levels. Thus, we recommend the use of olfactory bulbectomized rats as an animal model for investigating the effects and effect mechanisms of ultrasound exposure. NeuroReport 33: 445-449

Inaudible airborne ultrasound affects emotional states in the olfactory bulbectomized rat depression model

“…Olfactory bulbectomy was performed as previously described 4,12 . Brie y, rats were anesthetized using a mixed solution of medetomidine (2.4 mg/kg), midazolam (0.45 mg/kg), and butorphanol (3.0 mg/kg) dissolved in 0.9% saline and xed in a stereotactic apparatus.…”

“…The hyperemotionality of OBX rats at baseline and following the indicated intervention was evaluated using a hyperemotionality score 4,12,13 derived from the following behaviors: (1) attack response to a rod held in front of the snout, (2) startle response to air blown on the snout, (3) struggle response to handling with a gloved hand, and (4) ght response to a tail pitch delivered with mosquito forceps. Each response was graded as 0 (no reaction), 1 (slight), 2 (moderate), 3 (marked), or 4 (extreme).…”

“…The EPM test was conducted following 12 or 24 h in the aforementioned soundproof box with or without US exposure and 1 h of habituation. Tests were conducted as described in our previous study 4,14 . Brie y, the EPM apparatus was constructed of plastic and consisted of four 10 cm wide arms projecting in a cross pattern from a neutral central square and elevated 50 cm above the oor.…”

“…We recently reported that a 24-h exposure to high-frequency ultrasonic vocalizations (50 kHz USVs) or arti cial 50 kHz US reduced hyperemotionality in the olfactory bulbectomized (OBX) rat depression model, suggesting that this animal model is an appropriate for investigating the psychological effects of high-frequency sound 4 . However, since USVs are audible to rats, the observed emotional changes may have resulted from listening to the speaker's USVs or sounds of similar frequency.…”