Cold-Restraint Stress-Induced Ultrasonic Vocalization as a Novel Tool to Measure Anxiety in Mice

Yamauchi, Tsugumi; Yoshioka, Toshinori; Yamada, Daisuke; Hamano, Takumi; Ohashi, Misaki; Matsumoto, Maki; Iio, Keita; Ikeda, Maika; Kamei, Masato; Otsuki, Takaya; Sato, Yasuo; Nii, Kyoko; Suzuki, Masashi; Ichikawa, Hiroko; Nagase, Hiroshi; Iriyama, Satoshi; Yoshizawa, Kazumi; Nishino, Shoichi; Miyazaki, Satoru; Saitoh, Akiyoshi

doi:10.1248/bpb.b21-00776

Cited by 5 publications

(3 citation statements)

References 41 publications

(51 reference statements)

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“…Of note, based on these data and the fact that 35 µM of duloxetine has the capacity to exert significant inhibitory effects on platelet function regardless of the platelet function assay and/or agonist used, this dose was selected for further in vitro experimentation. Following this, we examined its ex vivo effects by injecting mice with 20 mg/kg of duloxetine, which was selected based on a literature review [ 16 , 17 , 18 , 19 , 20 , 21 ], before platelets were collected and their aggregation response examined. Indeed, duloxetine significantly reduced ADP- (58% ± 13), and U46619 (43% ± 11)-induced platelet aggregation ( Figure 1 C,D, respectively).…”

Section: Resultsmentioning

confidence: 99%

The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis

Lozano

Alarabi

Garcia

et al. 2022

IJMS

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While cardiovascular disease (CVD) is the leading cause of death, major depressive disorder (MDD) is the primary cause of disability, affecting more than 300 million people worldwide. Interestingly, there is evidence that CVD is more prevalent in people with MDD. It is well established that neurotransmitters, namely serotonin and norepinephrine, are involved in the biochemical mechanisms of MDD, and consequently, drugs targeting serotonin-norepinephrine reuptake, such as duloxetine, are commonly prescribed for MDD. In this connection, serotonin and norepinephrine are also known to play critical roles in primary hemostasis. Based on these considerations, we investigated if duloxetine can be repurposed as an antiplatelet medication. Our results-using human and/or mouse platelets show that duloxetine dose-dependently inhibited agonist-induced platelet aggregation, compared to the vehicle control. Furthermore, it also blocked agonist-induced dense and α-granule secretion, integrin αIIbβ3 activation, phosphatidylserine expression, and clot retraction. Moreover duloxetine-treated mice had a significantly prolonged occlusion time. Finally, duloxetine was also found to impair hemostasis. Collectively, our data indicate that the antidepressant duloxetine, which is a serotonin-norepinephrine antagonist, exerts antiplatelet and thromboprotective effects and inhibits hemostasis. Consequently, duloxetine, or a rationally designed derivative, presents potential benefits in the context of CVD, including that associated with MDD.

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Section: Resultsmentioning

confidence: 99%

The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis

Lozano

Alarabi

Garcia

et al. 2022

IJMS

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“…Administration of morphine that has a high affinity for mu-opioid receptors blocked anxiety-like behaviour caused by acute restraint (Anand et al, 2012). Similarly, the delta-opioid receptor agonist KNT-127 ameliorated the HPA axis response to cold restraint and freezing to the contextual CS (Yamada et Yamauchi et al, 2022). In contrast, stimulation of kappa-opioid receptors is thought to augment stress responses, as the kappa-opioid receptor agonist U50,488 increased anxiety-like behaviour in elevated plus maze tests (Bruchas et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Naloxone increases conditioned fear responses during social buffering in male rats

Yamasaki,

Kiyokawa,

Munetomo

et al. 2024

Eur J of Neuroscience

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Social buffering is the phenomenon in which the presence of an affiliative conspecific mitigates stress responses. We previously demonstrated that social buffering completely ameliorates conditioned fear responses in rats. However, the neuromodulators involved in social buffering are poorly understood. Given that opioids, dopamine, oxytocin and vasopressin play an important role in affiliative behaviour, here, we assessed the effects of the most well‐known antagonists, naloxone (opioid receptor antagonist), haloperidol (dopamine D2 receptor antagonist), atosiban (oxytocin receptor antagonist) and SR49059 (vasopressin V1a receptor antagonist), on social buffering. In Experiment 1, fear‐conditioned male subjects were intraperitoneally administered one of the four antagonists 25 min prior to exposure to a conditioned stimulus with an unfamiliar non‐conditioned rat. Naloxone, but not the other three antagonists, increased freezing and decreased walking and investigation as compared with saline administration. In Experiment 2, identical naloxone administration did not affect locomotor activity, anxiety‐like behaviour or freezing in an open‐field test. In Experiment 3, after confirming that the same naloxone administration again increased conditioned fear responses, as done in Experiment 1, we measured Fos expression in 16 brain regions. Compared with saline, naloxone increased Fos expression in the paraventricular nucleus of the hypothalamus and decreased Fos expression in the nucleus accumbens shell, anterior cingulate cortex and insular cortex and tended to decrease Fos expression in the nucleus accumbens core. Based on these results, we suggest that naloxone blocks social buffering of conditioned fear responses in male rats.

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“…Immediately after EPM tests, trunk blood samples were collected into tubes containing heparin. Plasma collection and measurement of plasma corticosterone levels were conducted according to methods reported in our previous study [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2022

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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

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Cold-Restraint Stress-Induced Ultrasonic Vocalization as a Novel Tool to Measure Anxiety in Mice

Cited by 5 publications

References 41 publications

The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis

The Antidepressant Duloxetine Inhibits Platelet Function and Protects against Thrombosis

Naloxone increases conditioned fear responses during social buffering in male rats

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

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