Long-lasting bradypnea induced by repeated social defeat

Abstract

peated social defeat in the rat induces long-lasting cardiovascular changes associated with anxiety. In this study, we investigated the effects of repeated social defeat on breathing. Respiratory rate was extracted from the respiratory sinus arrhythmia (RSA) peak frequency of the ECG in rats subjected to social defeat for 4 consecutive days. Respiratory rate was recorded under anesthesia 6 days (Dϩ10) or 26 days (Dϩ30) after social defeat. At Dϩ10, defeated (D) rats spent less time in the open arms of the elevated plus maze test, had heavier adrenal glands, and displayed bradypnea, unlike nondefeated animals. At Dϩ30, all signs of anxiety had disappeared. However, one-half of the rats still displayed bradypnea (D L rats, for low respiratory rate indicated by a lower RSA frequency), whereas those with higher respiratory rate (D H rats) had recovered. Acute blockade of the dorsomedial hypothalamus (DMH) or nucleus tractus solitarii (NTS) 5-HT 3 receptors reversed bradypnea in all D rats at Dϩ10 and in DL rats at Dϩ30. Respiratory rate was also recorded in conscious animals implanted with radiotelemetric ECG probes. DH rats recovered between Dϩ10 and Dϩ18, whereas DL rats remained bradypneic until Dϩ30. In conclusion, social stress induces sustained chronic bradypnea mediated by DMH neurons and NTS 5-HT3 receptors. These changes are associated with an anxiety-like state that persists until Dϩ10, followed by recovery. However, bradypnea may persist in one-half of the population up until Dϩ30, despite apparent recovery of the anxiety-like state.anxiety; breathing; serotonin; social defeat; telemetric recording BREATHING AND ANXIETY ARE intimately related (44). For example, respiratory distress and asphyxia are associated with dreadful feelings, and fear and anxiety can have profound effects on breathing. Clinical studies have shown that panic disorder, characterized by acute and unexpected anxiety attacks and substantial anxiety over the possibility of experiencing further attacks, is associated with symptoms including palpitations, shortness of breath, sweating, and hyperventilation (1). In addition, high levels of anxiety-related behavior in rats are associated with elevation of the resting respiratory rate (9). The respiratory rate also decreases during certain specific responses to stress, for instance during freezing behavior in the rat, when it is associated with ultrasonic vocalizations (19). However, much less is known about the long-term effects of emotional stress on breathing. In adult rats, intense neonatal emotional stress, such as maternal separation, can lead to a decrease in breathing rate during non-rapid-eye-movement sleep (24). A lower respiratory rate was also observed in anesthetized Flinder-Sensitive rats, a well-validated animal model of depression (33). However, respiratory rate does not appear to be altered in patients with major depression, although cardiovascular changes are observed (4). Clearly, more work needs to be done to understand the long-term effects of emotional stress on breathin...

Experimental social rejection increases dyspnoea perception and neural processing of respiratory sensations in healthy subjects

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A hypothalamo-midbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents

“…On the other hand, the DMH is also involved in the production of long-term bradypnea after social defeat (Brouillard et al, 2016). Considering that a reduction in chemoreflex tachypneic response induces a long-term hypoventilation (Hayward, 2001;Roux et al, 2000), we hypothesised that DMH may exert a long-term negative influence on the peripheral chemoreflex to reduce baseline respiratory values after stress condition.…”

“…generates a decrease in basal respiratory frequency, mediated by low and long-term DMHinduced NTS 5-HT 3a receptor stimulation (Brouillard et al, 2016). As a result of chemodenervation, basal breathing frequency is diminished (Hayward, 2001;Izumizaki et al, 2004).…”

“…Social defeat induces long-term bradypnea via NTS 5-HT 3 receptor activation (Brouillard et al, 2016). This suggests that these receptors may play a crucial role in the inhibition of the chemoreflex tachypnea.…”

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